<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:c7a5dfb9-1749-492e-b82b-7ebe2c8efca2,g:7145698d-a93c-4267-af3f-fad275474ecd-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/ConsolidatedStatementsofChangesinStockholdersEquity" xlink:type="simple" xlink:href="fold-20250331.xsd#ConsolidatedStatementsofChangesinStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/ConsolidatedStatementsofChangesinStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_c8aa5a99-46f7-40b4-a2fb-ec6c3671d1f0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_41238081-20e7-4de1-bda6-79d417dad1b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_c8aa5a99-46f7-40b4-a2fb-ec6c3671d1f0" xlink:to="loc_us-gaap_StatementTable_41238081-20e7-4de1-bda6-79d417dad1b2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_b5d37f33-140d-4693-9519-252b5d58f098" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_41238081-20e7-4de1-bda6-79d417dad1b2" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_b5d37f33-140d-4693-9519-252b5d58f098" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_b5d37f33-140d-4693-9519-252b5d58f098_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_b5d37f33-140d-4693-9519-252b5d58f098" xlink:to="loc_us-gaap_EquityComponentDomain_b5d37f33-140d-4693-9519-252b5d58f098_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_b5d37f33-140d-4693-9519-252b5d58f098" xlink:to="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_ef544476-5596-4962-aed5-4edd51914c34" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_CommonStockMember_ef544476-5596-4962-aed5-4edd51914c34" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_3f2f2b81-b262-4e06-98ef-759f3859f9ca" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_3f2f2b81-b262-4e06-98ef-759f3859f9ca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_793acd11-8a43-4fa1-af6b-4f6c97f70a7b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_WarrantMember_793acd11-8a43-4fa1-af6b-4f6c97f70a7b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonMember_fc79455c-ba89-4aa3-a6c6-4f6e7547e702" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockCommonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_TreasuryStockCommonMember_fc79455c-ba89-4aa3-a6c6-4f6e7547e702" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeMember_50fb5ff9-3909-4367-9ee1-2c20b07e5a4c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_ComprehensiveIncomeMember_50fb5ff9-3909-4367-9ee1-2c20b07e5a4c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_ace64ceb-d0b5-415c-95c8-55ff86c13e50" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_1283ea57-a130-4a5f-9920-e4397304198f" xlink:to="loc_us-gaap_RetainedEarningsMember_ace64ceb-d0b5-415c-95c8-55ff86c13e50" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_c8aa5a99-46f7-40b4-a2fb-ec6c3671d1f0" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_a005ef18-8f0c-4f0b-acd5-48a37a773ecd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_a005ef18-8f0c-4f0b-acd5-48a37a773ecd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_eabd3025-bb16-456b-b802-154a51cc7a88" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockholdersEquity_eabd3025-bb16-456b-b802-154a51cc7a88" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonShares_1d358896-f7b8-400e-a703-71f86c83e2c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockCommonShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_TreasuryStockCommonShares_1d358896-f7b8-400e-a703-71f86c83e2c5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_57007e15-9c7b-4474-8499-9f53ed9f2894" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_57007e15-9c7b-4474-8499-9f53ed9f2894" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_e8991bdd-4406-485f-b24d-fae3be9d6084" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_e8991bdd-4406-485f-b24d-fae3be9d6084" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_851c698f-546b-482f-999c-3f9f0d31b54d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardNetOfForfeitures_851c698f-546b-482f-999c-3f9f0d31b54d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures_9980fee4-344c-4dff-a9e8-6ed44ffed8d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardNetOfForfeitures_9980fee4-344c-4dff-a9e8-6ed44ffed8d6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_bc7169c8-ba72-4c4f-8fd5-a2000fd1a1fd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_bc7169c8-ba72-4c4f-8fd5-a2000fd1a1fd" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities_8754131d-b72c-49e1-81fe-2d06cd9018dd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesConversionOfConvertibleSecurities_8754131d-b72c-49e1-81fe-2d06cd9018dd" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueConversionOfConvertibleSecurities_73c04903-0900-4a38-be9c-aba265e0b593" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueConversionOfConvertibleSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueConversionOfConvertibleSecurities_73c04903-0900-4a38-be9c-aba265e0b593" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockSharesAcquired_9c03e4ee-be50-42fa-a776-7b12114cf369" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockSharesAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_TreasuryStockSharesAcquired_9c03e4ee-be50-42fa-a776-7b12114cf369" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockValueAcquiredCostMethod_a3b5b948-4a9c-4829-b7eb-1e255da3e074" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockValueAcquiredCostMethod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_TreasuryStockValueAcquiredCostMethod_a3b5b948-4a9c-4829-b7eb-1e255da3e074" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_5d998984-3546-41de-a4d4-c2d669ded51f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_5d998984-3546-41de-a4d4-c2d669ded51f" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_36dfe18b-134a-490d-95ce-70fc5cf86c2c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_36dfe18b-134a-490d-95ce-70fc5cf86c2c" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_28e52c16-f938-4034-946a-9c483a39486b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_d531b0ef-7d7e-4864-b75f-3c1fbe2c8aee" xlink:to="loc_us-gaap_NetIncomeLoss_28e52c16-f938-4034-946a-9c483a39486b" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_b752364c-36c2-4479-bd18-3f12cb525187" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_a6caf638-fec3-4b86-96a5-47d2e465be49" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonShares_a76939c0-3a35-4f46-a326-4af85aaf635b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockCommonShares"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/SummaryofSignificantAccountingPoliciesRevenuebyProductandGeographicalAreaDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#SummaryofSignificantAccountingPoliciesRevenuebyProductandGeographicalAreaDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/SummaryofSignificantAccountingPoliciesRevenuebyProductandGeographicalAreaDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_b283776e-69e6-4310-8be2-12ffa7bd3546" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_9a293cf7-1dcd-41dc-8688-c04f1016be62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_b283776e-69e6-4310-8be2-12ffa7bd3546" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_9a293cf7-1dcd-41dc-8688-c04f1016be62" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_3b897305-ba7e-413b-87b6-8fdf9f018adb" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_9a293cf7-1dcd-41dc-8688-c04f1016be62" xlink:to="loc_srt_StatementGeographicalAxis_3b897305-ba7e-413b-87b6-8fdf9f018adb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_3b897305-ba7e-413b-87b6-8fdf9f018adb_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_3b897305-ba7e-413b-87b6-8fdf9f018adb" xlink:to="loc_srt_SegmentGeographicalDomain_3b897305-ba7e-413b-87b6-8fdf9f018adb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_22aa78f7-1af7-49d3-85e8-796784f59943" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_3b897305-ba7e-413b-87b6-8fdf9f018adb" xlink:to="loc_srt_SegmentGeographicalDomain_22aa78f7-1af7-49d3-85e8-796784f59943" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_country_US_07db7447-7c8a-4a05-8a4a-b6dcef5c7ea8" xlink:href="https://xbrl.sec.gov/country/2024/country-2024.xsd#country_US"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_22aa78f7-1af7-49d3-85e8-796784f59943" xlink:to="loc_country_US_07db7447-7c8a-4a05-8a4a-b6dcef5c7ea8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonUsMember_98b18dd4-7dfd-44be-b799-d3045451b611" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NonUsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_22aa78f7-1af7-49d3-85e8-796784f59943" xlink:to="loc_us-gaap_NonUsMember_98b18dd4-7dfd-44be-b799-d3045451b611" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_3534b8f4-6aa4-4bdb-9529-8b4858a98832" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_9a293cf7-1dcd-41dc-8688-c04f1016be62" xlink:to="loc_srt_ProductOrServiceAxis_3534b8f4-6aa4-4bdb-9529-8b4858a98832" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_3534b8f4-6aa4-4bdb-9529-8b4858a98832_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_3534b8f4-6aa4-4bdb-9529-8b4858a98832" xlink:to="loc_srt_ProductsAndServicesDomain_3534b8f4-6aa4-4bdb-9529-8b4858a98832_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_2e85c510-c700-48c0-bdf7-03958a2aee02" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_3534b8f4-6aa4-4bdb-9529-8b4858a98832" xlink:to="loc_srt_ProductsAndServicesDomain_2e85c510-c700-48c0-bdf7-03958a2aee02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_GalafoldMember_367b2434-f581-4e1a-b3ec-d2e3c13639e6" xlink:href="fold-20250331.xsd#fold_GalafoldMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_2e85c510-c700-48c0-bdf7-03958a2aee02" xlink:to="loc_fold_GalafoldMember_367b2434-f581-4e1a-b3ec-d2e3c13639e6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_PombilitiOpfoldaMember_10334c42-a3da-4419-9038-9ad9d2816c07" xlink:href="fold-20250331.xsd#fold_PombilitiOpfoldaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_2e85c510-c700-48c0-bdf7-03958a2aee02" xlink:to="loc_fold_PombilitiOpfoldaMember_10334c42-a3da-4419-9038-9ad9d2816c07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_d5f7182b-9192-4151-8b48-309e0d58be59" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_b283776e-69e6-4310-8be2-12ffa7bd3546" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_d5f7182b-9192-4151-8b48-309e0d58be59" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/CashCashEquivalentsMarketableSecuritiesandRestrictedCashCashandAvailableforSaleSecuritiesDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#CashCashEquivalentsMarketableSecuritiesandRestrictedCashCashandAvailableforSaleSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/CashCashEquivalentsMarketableSecuritiesandRestrictedCashCashandAvailableforSaleSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_099797e3-0a89-4f0b-b537-c8ef6df860a0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_099797e3-0a89-4f0b-b537-c8ef6df860a0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_8ba4b993-744f-401b-a66e-9afedd75455c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_099797e3-0a89-4f0b-b537-c8ef6df860a0" xlink:to="loc_us-gaap_FinancialInstrumentAxis_8ba4b993-744f-401b-a66e-9afedd75455c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8ba4b993-744f-401b-a66e-9afedd75455c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8ba4b993-744f-401b-a66e-9afedd75455c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_8ba4b993-744f-401b-a66e-9afedd75455c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_8ba4b993-744f-401b-a66e-9afedd75455c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_33b34186-1084-46ee-a4d4-16482528a101" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_33b34186-1084-46ee-a4d4-16482528a101" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_322ddd00-ea95-421d-869e-ce7eced244c4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_322ddd00-ea95-421d-869e-ce7eced244c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_96b51b12-e3c5-48ed-9f9e-0be4661f0369" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_96b51b12-e3c5-48ed-9f9e-0be4661f0369" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_4acbbc8c-be6a-43b6-9d16-d4cf74c04be1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:to="loc_us-gaap_MoneyMarketFundsMember_4acbbc8c-be6a-43b6-9d16-d4cf74c04be1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_95556089-02e6-4ad3-a549-1a319c85dcde" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_bb3408b7-b259-433f-820b-6644fbb2bb0d" xlink:to="loc_us-gaap_CertificatesOfDepositMember_95556089-02e6-4ad3-a549-1a319c85dcde" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_0408b252-8c7c-4fda-afc1-59f29da35bf5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_0408b252-8c7c-4fda-afc1-59f29da35bf5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_aeda9727-9f82-40e9-8d7e-a7566d784a5d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_aeda9727-9f82-40e9-8d7e-a7566d784a5d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_b511a8e4-5a7b-403d-ac32-918a3e015a08" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_b511a8e4-5a7b-403d-ac32-918a3e015a08" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_0b0e96e2-a576-4c80-8af9-9bedd6a1bae4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_0b0e96e2-a576-4c80-8af9-9bedd6a1bae4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_9b4d3565-841f-4857-82b7-0a831cc8aa24" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_9b4d3565-841f-4857-82b7-0a831cc8aa24" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_e64a954e-79e7-4d24-9437-091aeaaf1916" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_e64a954e-79e7-4d24-9437-091aeaaf1916" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecurities_e0dcdc8f-af42-421d-b290-1b52847939c3" xlink:href="fold-20250331.xsd#fold_CashCashEquivalentsAndAvailableforsaleDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecurities_e0dcdc8f-af42-421d-b290-1b52847939c3" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_a14f2691-0214-4186-bc4f-77e8118dc1d0" xlink:href="fold-20250331.xsd#fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_a14f2691-0214-4186-bc4f-77e8118dc1d0" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_ece27e10-6cb5-447d-9129-e4bb8aedff6e" xlink:href="fold-20250331.xsd#fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_ece27e10-6cb5-447d-9129-e4bb8aedff6e" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesFairValueDisclosure_7a8d3d66-b040-41a9-a4bb-49a0dfa71e2b" xlink:href="fold-20250331.xsd#fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_dcd436a3-2d94-41cc-a62d-a89f6b558332" xlink:to="loc_fold_CashCashEquivalentsAndAvailableforsaleDebtSecuritiesFairValueDisclosure_7a8d3d66-b040-41a9-a4bb-49a0dfa71e2b" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/DebtSummaryofLongTermDebtDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#DebtSummaryofLongTermDebtDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/DebtSummaryofLongTermDebtDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_ce7407d5-d3aa-4beb-b88f-2d0891f1db28" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:to="loc_us-gaap_DebtInstrumentTable_ce7407d5-d3aa-4beb-b88f-2d0891f1db28" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_6dd4f999-4b1e-48f6-b97f-b910d68451b9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_ce7407d5-d3aa-4beb-b88f-2d0891f1db28" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_6dd4f999-4b1e-48f6-b97f-b910d68451b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_6dd4f999-4b1e-48f6-b97f-b910d68451b9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_6dd4f999-4b1e-48f6-b97f-b910d68451b9" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_6dd4f999-4b1e-48f6-b97f-b910d68451b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_cd90a9ff-1b7c-4ec0-9c41-69231b5c90cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_6dd4f999-4b1e-48f6-b97f-b910d68451b9" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_cd90a9ff-1b7c-4ec0-9c41-69231b5c90cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeniorLoansMember_980b03cd-9beb-42bb-bcf7-f9d9421c6c8c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SeniorLoansMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_cd90a9ff-1b7c-4ec0-9c41-69231b5c90cb" xlink:to="loc_us-gaap_SeniorLoansMember_980b03cd-9beb-42bb-bcf7-f9d9421c6c8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_ce7407d5-d3aa-4beb-b88f-2d0891f1db28" xlink:to="loc_us-gaap_DebtInstrumentAxis_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_11bcf910-7808-428e-bac4-bc3e7ccf6c39" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_5f6c3f3f-8118-42c4-9f94-5d9d813ece5d" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_11bcf910-7808-428e-bac4-bc3e7ccf6c39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_SeniorSecuredTermLoanDue2029Member_3c0131b5-cab8-4015-9204-a0042a352a83" xlink:href="fold-20250331.xsd#fold_SeniorSecuredTermLoanDue2029Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_11bcf910-7808-428e-bac4-bc3e7ccf6c39" xlink:to="loc_fold_SeniorSecuredTermLoanDue2029Member_3c0131b5-cab8-4015-9204-a0042a352a83" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_0712af29-6739-4449-b0b6-f8fa8072ffaf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_0712af29-6739-4449-b0b6-f8fa8072ffaf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscount_7fffedc8-0bc0-4b17-b8e6-997d293144c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentUnamortizedDiscount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscount_7fffedc8-0bc0-4b17-b8e6-997d293144c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredOfferingCosts_eec8a3b1-bcc2-454a-9edc-cfe306f469ac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredOfferingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:to="loc_us-gaap_DeferredOfferingCosts_eec8a3b1-bcc2-454a-9edc-cfe306f469ac" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_a02e640e-bf7d-4a59-b183-b68ac2767ab8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_c8153a45-f902-47b8-a7de-b4f80f4c13ee" xlink:to="loc_us-gaap_LongTermDebt_a02e640e-bf7d-4a59-b183-b68ac2767ab8" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/StockBasedCompensationWeightedaverageAssumptionsDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#StockBasedCompensationWeightedaverageAssumptionsDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/StockBasedCompensationWeightedaverageAssumptionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_430f46d1-005b-40c8-9923-76982ae6b64e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_430f46d1-005b-40c8-9923-76982ae6b64e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_430f46d1-005b-40c8-9923-76982ae6b64e" xlink:to="loc_us-gaap_AwardTypeAxis_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d167a9c4-90f6-4d5b-962f-99346d536709" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_a369187c-d6a9-42fe-8c1e-ffd80ae5a44e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d167a9c4-90f6-4d5b-962f-99346d536709" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_04678b93-26e5-4c79-804a-6666687007e8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_d167a9c4-90f6-4d5b-962f-99346d536709" xlink:to="loc_us-gaap_EmployeeStockOptionMember_04678b93-26e5-4c79-804a-6666687007e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_cba0b804-c893-4492-bce1-48a5a41f0459" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_cba0b804-c893-4492-bce1-48a5a41f0459" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_f3e0e54e-fb62-462f-a5e9-aaff6be1bced" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_f3e0e54e-fb62-462f-a5e9-aaff6be1bced" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_13a9cc57-fa71-4f79-85bf-b1c43c0918d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_13a9cc57-fa71-4f79-85bf-b1c43c0918d8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendPerShare_d7b1c679-612c-44a4-8683-266b70d65478" xlink:href="fold-20250331.xsd#fold_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_db3fab7e-f04c-4073-9e41-0534733fbeb8" xlink:to="loc_fold_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendPerShare_d7b1c679-612c-44a4-8683-266b70d65478" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/StockBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#StockBasedCompensationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/StockBasedCompensationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01588f82-5ce8-4e41-b5c5-8d99291f81b9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f0e5dae9-c84d-434b-94fc-1a87ee77f049" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01588f82-5ce8-4e41-b5c5-8d99291f81b9" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f0e5dae9-c84d-434b-94fc-1a87ee77f049" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_68c875e3-a092-4af7-980c-694d4dd05b0b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_f0e5dae9-c84d-434b-94fc-1a87ee77f049" xlink:to="loc_us-gaap_AwardTypeAxis_68c875e3-a092-4af7-980c-694d4dd05b0b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_68c875e3-a092-4af7-980c-694d4dd05b0b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_68c875e3-a092-4af7-980c-694d4dd05b0b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_68c875e3-a092-4af7-980c-694d4dd05b0b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8d1bb533-b2ba-4d0b-8a47-57abe584fc2e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_68c875e3-a092-4af7-980c-694d4dd05b0b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8d1bb533-b2ba-4d0b-8a47-57abe584fc2e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_0c417090-8f28-4c02-aeb4-88223fb7924f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8d1bb533-b2ba-4d0b-8a47-57abe584fc2e" xlink:to="loc_us-gaap_EmployeeStockOptionMember_0c417090-8f28-4c02-aeb4-88223fb7924f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_eaaff4d3-e236-4a47-afa6-a8e1fb20c5a6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_8d1bb533-b2ba-4d0b-8a47-57abe584fc2e" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_eaaff4d3-e236-4a47-afa6-a8e1fb20c5a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_e42616fd-0e23-4804-b953-a28ca3e22810" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01588f82-5ce8-4e41-b5c5-8d99291f81b9" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_e42616fd-0e23-4804-b953-a28ca3e22810" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_ecdcff0b-310c-4366-954f-79d55ed77db7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_01588f82-5ce8-4e41-b5c5-8d99291f81b9" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_ecdcff0b-310c-4366-954f-79d55ed77db7" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/StockBasedCompensationRSUsandPBRSUsSummaryDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#StockBasedCompensationRSUsandPBRSUsSummaryDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/StockBasedCompensationRSUsandPBRSUsSummaryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_68249ea0-e362-4ea8-bd82-9004ae7a65bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ad225e1a-4f4d-4e15-8590-16bb9d606681" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_68249ea0-e362-4ea8-bd82-9004ae7a65bb" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ad225e1a-4f4d-4e15-8590-16bb9d606681" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_f694b80e-b46a-487d-a7d3-0e5b2995cabc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ad225e1a-4f4d-4e15-8590-16bb9d606681" xlink:to="loc_us-gaap_AwardTypeAxis_f694b80e-b46a-487d-a7d3-0e5b2995cabc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f694b80e-b46a-487d-a7d3-0e5b2995cabc_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_f694b80e-b46a-487d-a7d3-0e5b2995cabc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f694b80e-b46a-487d-a7d3-0e5b2995cabc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_baf50928-9e1b-4d6f-9458-20b480439552" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_f694b80e-b46a-487d-a7d3-0e5b2995cabc" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_baf50928-9e1b-4d6f-9458-20b480439552" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_08b1d700-6695-418e-a2cb-51ceffd5bc67" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_baf50928-9e1b-4d6f-9458-20b480439552" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_08b1d700-6695-418e-a2cb-51ceffd5bc67" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_68249ea0-e362-4ea8-bd82-9004ae7a65bb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_403ec2bf-aa24-4521-930c-47cc2b5136ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_403ec2bf-aa24-4521-930c-47cc2b5136ec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_adc49fbe-9bf9-4266-b96b-23e2300a4ac3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_adc49fbe-9bf9-4266-b96b-23e2300a4ac3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_65d593e7-74ea-43d6-8484-d85cb1cc460b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_65d593e7-74ea-43d6-8484-d85cb1cc460b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_505bc848-ecef-4f47-8aeb-2aa8ae471780" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_7fddc126-a819-491c-b98a-fecd308c26af" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_505bc848-ecef-4f47-8aeb-2aa8ae471780" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_5476c1f0-3d7f-4492-9610-e24bd8ade8ef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_68249ea0-e362-4ea8-bd82-9004ae7a65bb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_65893de8-d018-46cf-a866-1a3b7b16f830" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_65893de8-d018-46cf-a866-1a3b7b16f830" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_c660efe8-fa0f-461b-8ea6-bc9790b661ef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_c660efe8-fa0f-461b-8ea6-bc9790b661ef" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_065e4625-bf9d-4c75-a12c-b4abcbc6f27a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_065e4625-bf9d-4c75-a12c-b4abcbc6f27a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_823447ac-6a37-4424-9d45-daabab4d07b8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_86259474-0a9b-4792-b829-28c626ecf43a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_823447ac-6a37-4424-9d45-daabab4d07b8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_c8d9743a-dea4-49aa-a3bf-a0b1273c6589" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract_67c6a9cf-4ef7-4bc8-bf45-d6c3ab081dfd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_68249ea0-e362-4ea8-bd82-9004ae7a65bb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract_67c6a9cf-4ef7-4bc8-bf45-d6c3ab081dfd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsOutstandingWeightedAverageRemainingContractualTerms_c2b46ad8-7414-4370-b17e-3e31d2f9c668" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsOutstandingWeightedAverageRemainingContractualTerms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract_67c6a9cf-4ef7-4bc8-bf45-d6c3ab081dfd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsOutstandingWeightedAverageRemainingContractualTerms_c2b46ad8-7414-4370-b17e-3e31d2f9c668" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueNonvested_a286db59-0f4d-40da-b6d6-7fac001ff1a6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueNonvested"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsAdditionalDisclosuresAbstract_67c6a9cf-4ef7-4bc8-bf45-d6c3ab081dfd" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardEquityInstrumentsOtherThanOptionsAggregateIntrinsicValueNonvested_a286db59-0f4d-40da-b6d6-7fac001ff1a6" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/StockBasedCompensationExpenseSummaryDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#StockBasedCompensationExpenseSummaryDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/StockBasedCompensationExpenseSummaryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_87991954-14b8-491b-b374-f75a3800a0bd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb4da4d3-4ab8-4d07-b805-cc93a18849f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_87991954-14b8-491b-b374-f75a3800a0bd" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb4da4d3-4ab8-4d07-b805-cc93a18849f6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_eb41284b-5dbc-4ffe-9528-429ae273b44d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_eb4da4d3-4ab8-4d07-b805-cc93a18849f6" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_eb41284b-5dbc-4ffe-9528-429ae273b44d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_eb41284b-5dbc-4ffe-9528-429ae273b44d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_eb41284b-5dbc-4ffe-9528-429ae273b44d" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_eb41284b-5dbc-4ffe-9528-429ae273b44d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_a51309b2-fcfa-4dde-8890-362c6e38269f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_eb41284b-5dbc-4ffe-9528-429ae273b44d" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_a51309b2-fcfa-4dde-8890-362c6e38269f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_4bd9f964-6c4f-4414-ba93-2a6e4f134740" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_a51309b2-fcfa-4dde-8890-362c6e38269f" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_4bd9f964-6c4f-4414-ba93-2a6e4f134740" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_26d01879-ae01-4d62-9acb-9738bea48f6c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_a51309b2-fcfa-4dde-8890-362c6e38269f" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_26d01879-ae01-4d62-9acb-9738bea48f6c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_59b288cd-72ec-4cd6-b2ee-9f4fc667b67c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_87991954-14b8-491b-b374-f75a3800a0bd" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_59b288cd-72ec-4cd6-b2ee-9f4fc667b67c" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/AssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#AssetsandLiabilitiesMeasuredatFairValueDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/AssetsandLiabilitiesMeasuredatFairValueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2d4024a5-aaa3-4f0f-b950-0322e27360c2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_6380e82a-0c01-49a1-b224-7aba8e5380b9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2d4024a5-aaa3-4f0f-b950-0322e27360c2" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_6380e82a-0c01-49a1-b224-7aba8e5380b9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b1042d75-ad9e-45da-8fd2-c81cf8984295" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_6380e82a-0c01-49a1-b224-7aba8e5380b9" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b1042d75-ad9e-45da-8fd2-c81cf8984295" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_b1042d75-ad9e-45da-8fd2-c81cf8984295_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b1042d75-ad9e-45da-8fd2-c81cf8984295" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_b1042d75-ad9e-45da-8fd2-c81cf8984295_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_69992b11-7cd8-4bd0-9aa8-0bef11c95bb7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_b1042d75-ad9e-45da-8fd2-c81cf8984295" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_69992b11-7cd8-4bd0-9aa8-0bef11c95bb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_f9155c09-42e2-4597-8de0-db3aa32f6d16" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_69992b11-7cd8-4bd0-9aa8-0bef11c95bb7" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_f9155c09-42e2-4597-8de0-db3aa32f6d16" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_8c8d4d5a-5b37-4718-83d2-807c2b0d59a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_69992b11-7cd8-4bd0-9aa8-0bef11c95bb7" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_8c8d4d5a-5b37-4718-83d2-807c2b0d59a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_810dc054-6e8d-4c77-9d89-ef577c0dea25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_6380e82a-0c01-49a1-b224-7aba8e5380b9" xlink:to="loc_us-gaap_FinancialInstrumentAxis_810dc054-6e8d-4c77-9d89-ef577c0dea25" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_810dc054-6e8d-4c77-9d89-ef577c0dea25_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_810dc054-6e8d-4c77-9d89-ef577c0dea25" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_810dc054-6e8d-4c77-9d89-ef577c0dea25_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_810dc054-6e8d-4c77-9d89-ef577c0dea25" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_2512d8d1-2de0-45d0-9211-187038d6558a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:to="loc_us-gaap_CommercialPaperNotIncludedWithCashAndCashEquivalentsMember_2512d8d1-2de0-45d0-9211-187038d6558a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_589482ac-fda3-415c-acb9-6abaed3dd928" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_589482ac-fda3-415c-acb9-6abaed3dd928" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_85a7e30d-4f9c-4cb7-9e40-1053a5157555" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_85a7e30d-4f9c-4cb7-9e40-1053a5157555" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_52d902bf-e86a-428c-91f5-064c54b92f2b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_fceb1718-0dcb-4990-9154-a1118c72f3e0" xlink:to="loc_us-gaap_MoneyMarketFundsMember_52d902bf-e86a-428c-91f5-064c54b92f2b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_1ebd9e8d-1d56-4008-87cf-9c487bb99e83" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2d4024a5-aaa3-4f0f-b950-0322e27360c2" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_1ebd9e8d-1d56-4008-87cf-9c487bb99e83" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_988e069b-e3a6-4af3-bb06-5d8a22b66516" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_1ebd9e8d-1d56-4008-87cf-9c487bb99e83" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_988e069b-e3a6-4af3-bb06-5d8a22b66516" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_406f0aae-db39-42d2-b9c9-7b9c64026849" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_2d4024a5-aaa3-4f0f-b950-0322e27360c2" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_406f0aae-db39-42d2-b9c9-7b9c64026849" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredCompensationSharebasedArrangementsLiabilityCurrentAndNoncurrent_136098cd-9dbc-45c5-96fa-b37963c8a60d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredCompensationSharebasedArrangementsLiabilityCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_406f0aae-db39-42d2-b9c9-7b9c64026849" xlink:to="loc_us-gaap_DeferredCompensationSharebasedArrangementsLiabilityCurrentAndNoncurrent_136098cd-9dbc-45c5-96fa-b37963c8a60d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_73072c21-891e-4bb9-a499-aac8a56af7d1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_406f0aae-db39-42d2-b9c9-7b9c64026849" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_73072c21-891e-4bb9-a499-aac8a56af7d1" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/BasicandDilutedNetLossperCommonShareDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#BasicandDilutedNetLossperCommonShareDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/BasicandDilutedNetLossperCommonShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_b84c5e3b-94b8-4c78-a2ff-06928b7b12cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_161966a7-acb0-429c-b07e-73aa41f88840" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_b84c5e3b-94b8-4c78-a2ff-06928b7b12cb" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_161966a7-acb0-429c-b07e-73aa41f88840" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_4ea98c9e-5515-4220-a71e-e0cb76b23740" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_161966a7-acb0-429c-b07e-73aa41f88840" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_4ea98c9e-5515-4220-a71e-e0cb76b23740" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_4ea98c9e-5515-4220-a71e-e0cb76b23740_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_4ea98c9e-5515-4220-a71e-e0cb76b23740" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_4ea98c9e-5515-4220-a71e-e0cb76b23740_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_2a615eff-969d-4319-bdb2-caaf01365bbf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_4ea98c9e-5515-4220-a71e-e0cb76b23740" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_2a615eff-969d-4319-bdb2-caaf01365bbf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_f4e195f8-3940-403a-bb04-6135097694e7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_2a615eff-969d-4319-bdb2-caaf01365bbf" xlink:to="loc_us-gaap_EmployeeStockOptionMember_f4e195f8-3940-403a-bb04-6135097694e7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_73e37d32-b242-48d5-bd5b-95b6067fcabe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_2a615eff-969d-4319-bdb2-caaf01365bbf" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_73e37d32-b242-48d5-bd5b-95b6067fcabe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_d6280855-6f2c-4a03-9291-2a0fe9c6c054" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_b84c5e3b-94b8-4c78-a2ff-06928b7b12cb" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_d6280855-6f2c-4a03-9291-2a0fe9c6c054" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.amicustherapeutics.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="fold-20250331.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.amicustherapeutics.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_8166bf73-1c91-4c64-b0dd-3a1465886ef8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_8166bf73-1c91-4c64-b0dd-3a1465886ef8" xlink:to="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_28eeeb03-8d1e-41bf-864f-b0a0d9d298da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_28eeeb03-8d1e-41bf-864f-b0a0d9d298da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_28eeeb03-8d1e-41bf-864f-b0a0d9d298da_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_28eeeb03-8d1e-41bf-864f-b0a0d9d298da" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_28eeeb03-8d1e-41bf-864f-b0a0d9d298da_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_43dabf33-e469-497f-ba5e-f3b04e7929c8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_28eeeb03-8d1e-41bf-864f-b0a0d9d298da" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_43dabf33-e469-497f-ba5e-f3b04e7929c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_285435f5-df1a-49f1-aa3a-e960e148e1e2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_43dabf33-e469-497f-ba5e-f3b04e7929c8" xlink:to="loc_us-gaap_SubsequentEventMember_285435f5-df1a-49f1-aa3a-e960e148e1e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_c5de206f-09e6-4a44-a850-523a057ff5ec" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:to="loc_srt_CounterpartyNameAxis_c5de206f-09e6-4a44-a850-523a057ff5ec" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c5de206f-09e6-4a44-a850-523a057ff5ec_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_c5de206f-09e6-4a44-a850-523a057ff5ec" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c5de206f-09e6-4a44-a850-523a057ff5ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_77ac5c1f-eaa4-465d-87ae-f47e5133f2f5" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_c5de206f-09e6-4a44-a850-523a057ff5ec" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_77ac5c1f-eaa4-465d-87ae-f47e5133f2f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_DimerixLimitedMember_668f8c4e-b654-45ce-911b-8d77c62df383" xlink:href="fold-20250331.xsd#fold_DimerixLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_77ac5c1f-eaa4-465d-87ae-f47e5133f2f5" xlink:to="loc_fold_DimerixLimitedMember_668f8c4e-b654-45ce-911b-8d77c62df383" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_LicensingAgreementMilestoneAxis_f176cdc1-a877-422b-a09b-16dad8cfe91b" xlink:href="fold-20250331.xsd#fold_LicensingAgreementMilestoneAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:to="loc_fold_LicensingAgreementMilestoneAxis_f176cdc1-a877-422b-a09b-16dad8cfe91b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_LicensingAgreementMilestoneDomain_f176cdc1-a877-422b-a09b-16dad8cfe91b_default" xlink:href="fold-20250331.xsd#fold_LicensingAgreementMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_fold_LicensingAgreementMilestoneAxis_f176cdc1-a877-422b-a09b-16dad8cfe91b" xlink:to="loc_fold_LicensingAgreementMilestoneDomain_f176cdc1-a877-422b-a09b-16dad8cfe91b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_LicensingAgreementMilestoneDomain_7f15260f-fdc1-4471-80aa-61ceabdd3ad6" xlink:href="fold-20250331.xsd#fold_LicensingAgreementMilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_fold_LicensingAgreementMilestoneAxis_f176cdc1-a877-422b-a09b-16dad8cfe91b" xlink:to="loc_fold_LicensingAgreementMilestoneDomain_7f15260f-fdc1-4471-80aa-61ceabdd3ad6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_SuccessBasedDevelopmentAndRegulatoryMilestoneMember_b5370ca7-1896-4621-bef6-c90d6cfe72aa" xlink:href="fold-20250331.xsd#fold_SuccessBasedDevelopmentAndRegulatoryMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_fold_LicensingAgreementMilestoneDomain_7f15260f-fdc1-4471-80aa-61ceabdd3ad6" xlink:to="loc_fold_SuccessBasedDevelopmentAndRegulatoryMilestoneMember_b5370ca7-1896-4621-bef6-c90d6cfe72aa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_CommercialMilestoneMember_cc05e0d7-caad-47cd-bbf5-5f6fdd4367cc" xlink:href="fold-20250331.xsd#fold_CommercialMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_fold_LicensingAgreementMilestoneDomain_7f15260f-fdc1-4471-80aa-61ceabdd3ad6" xlink:to="loc_fold_CommercialMilestoneMember_cc05e0d7-caad-47cd-bbf5-5f6fdd4367cc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_316c3272-9609-4568-b87c-d59b45002054" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_b8fede68-7ee2-4588-8d58-25acffcd38db" xlink:to="loc_srt_ProductOrServiceAxis_316c3272-9609-4568-b87c-d59b45002054" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_316c3272-9609-4568-b87c-d59b45002054_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_316c3272-9609-4568-b87c-d59b45002054" xlink:to="loc_srt_ProductsAndServicesDomain_316c3272-9609-4568-b87c-d59b45002054_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_bbdd174e-7510-44b5-9a1a-c57ea1a25ac4" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_316c3272-9609-4568-b87c-d59b45002054" xlink:to="loc_srt_ProductsAndServicesDomain_bbdd174e-7510-44b5-9a1a-c57ea1a25ac4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicenseMember_ca9eddbc-e28e-4684-9a4b-6222fd69da6a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LicenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_bbdd174e-7510-44b5-9a1a-c57ea1a25ac4" xlink:to="loc_us-gaap_LicenseMember_ca9eddbc-e28e-4684-9a4b-6222fd69da6a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_8848c812-607c-46ca-9f02-b08538fc4d4f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_8166bf73-1c91-4c64-b0dd-3a1465886ef8" xlink:to="loc_us-gaap_ContractWithCustomerLiability_8848c812-607c-46ca-9f02-b08538fc4d4f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_RevenueRemainingPerformanceObligationVariableConsiderationAmount_6fa6881d-757d-444f-b101-75795f9d49c7" xlink:href="fold-20250331.xsd#fold_RevenueRemainingPerformanceObligationVariableConsiderationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_8166bf73-1c91-4c64-b0dd-3a1465886ef8" xlink:to="loc_fold_RevenueRemainingPerformanceObligationVariableConsiderationAmount_6fa6881d-757d-444f-b101-75795f9d49c7" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_MargaretG.McGlynnMember_7ee4e72e-b42b-4006-8ce0-b620b5f94027" xlink:href="fold-20250331.xsd#fold_MargaretG.McGlynnMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_fold_MargaretG.McGlynnMember_7ee4e72e-b42b-4006-8ce0-b620b5f94027" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_DavidClarkMember_f5b59b41-c25f-4e02-801e-df835664ba59" xlink:href="fold-20250331.xsd#fold_DavidClarkMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_fold_DavidClarkMember_f5b59b41-c25f-4e02-801e-df835664ba59" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/TradingArrangementsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#TradingArrangmentsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/TradingArrangementsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllTradingArrangementsMember" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllTradingArrangementsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_MargaretG.McGlynnTradingArrangementStockOptionsMember_333a71ef-f03a-4216-97c3-7f9b986ffbb7" xlink:href="fold-20250331.xsd#fold_MargaretG.McGlynnTradingArrangementStockOptionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllTradingArrangementsMember" xlink:to="loc_fold_MargaretG.McGlynnTradingArrangementStockOptionsMember_333a71ef-f03a-4216-97c3-7f9b986ffbb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_fold_MargaretG.McGlynnTradingArrangementCommonStockUnderlyingStockOptionsMember_5d57e8e4-eb80-447b-adc7-ad1effcb11d4" xlink:href="fold-20250331.xsd#fold_MargaretG.McGlynnTradingArrangementCommonStockUnderlyingStockOptionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllTradingArrangementsMember" xlink:to="loc_fold_MargaretG.McGlynnTradingArrangementCommonStockUnderlyingStockOptionsMember_5d57e8e4-eb80-447b-adc7-ad1effcb11d4" xlink:type="arc" order="2"/>
  </link:definitionLink>
</link:linkbase>
