Fabry disease - Wikipedia

Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, ... Fabrydisease FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Rarehumangeneticlysosomalstoragedisorder MedicalconditionFabrydiseaseOthernamesFabry'sdisease,Anderson–Fabrydisease,angiokeratomacorporisdiffusum,alpha-galactosidaseAdeficiencyAlphagalactosidase-thedeficientproteininFabrydiseasePronunciation/ˈfɑːbri/SpecialtyEndocrinology,cardiology,nephrology,dermatologyComplicationsHeartfailure,abnormalheartrhythmsUsualonsetChildhoodCausesGeneticDiagnosticmethodEnzymeactivityassay,genetictestingDifferentialdiagnosisHypertrophiccardiomyopathyTreatmentEnzymereplacement Fabrydisease,alsoknownasAnderson–Fabrydisease,isararegeneticdiseasethatcanaffectmanypartsofthebody,includingthekidneys,heart,andskin.[1]Fabrydiseaseisoneofagroupofconditionsknownaslysosomalstoragediseases.ThegeneticmutationthatcausesFabrydiseaseinterfereswiththefunctionofanenzymethatprocessesbiomoleculesknownassphingolipids,leadingtothesesubstancesbuildingupinthewallsofbloodvesselsandotherorgans.ItisinheritedinanX-linkedmanner. Fabrydiseaseissometimesdiagnosedusingabloodtestthatmeasurestheactivityoftheaffectedenzymecalledalpha-galactosidase,butgenetictestingisalsosometimesused,particularlyinfemales. ThetreatmentforFabrydiseasevariesdependingontheorgansaffectedbythecondition,andtheunderlyingcausecanbeaddressedbyreplacingtheenzymethatislacking. ThefirstdescriptionsoftheconditionweremadesimultaneouslybydermatologistJohannesFabry[2]andthesurgeonWilliamAnderson[3]in1898.[4] Contents 1Signsandsymptoms 1.1Pain 1.2Kidney 1.3Heart 1.4Skin 1.5Othermanifestations 2Causes 3Mechanism 4Diagnosis 5Treatment 5.1Therapiestargetingenzymeactivity 5.2Organ-specifictreatment 6Prognosis 7Epidemiology 8Research 9History 10Societyandculture 11Seealso 12References 12.1Furtherreading 13Externallinks Signsandsymptoms[edit] Abilateral,whorl-likecornealpatternofcream-coloredlinesinapersonwithFabrydisease Angiokeratoma,acommonskinmanifestationinFabrydisease Symptomsaretypicallyfirstexperiencedinearlychildhoodandcanbeverydifficulttodiagnose;therarityofFabrydiseasetomanyclinicianssometimesleadstomisdiagnoses.Manifestationsofthediseaseusuallyincreaseinnumberandseverityasanindividualages.[5] Pain[edit] Full-bodyorlocalizedpaintotheextremities(knownasacroparesthesia)orgastrointestinal(GI)tractiscommoninpatientswithFabrydisease.Thispaincanincreaseovertime.Thisacroparesthesiaisbelievedtoberelatedtothedamageofperipheralnervefibersthattransmitpain.GI-tractpainislikelycausedbyaccumulationoflipidsinthesmallvasculatureoftheGItract,whichobstructsbloodflowandcausespain.[6] Kidney[edit] Kidneycomplicationsarecommonandseriouseffectsofthedisease;chronickidneydiseaseandkidneyfailuremayworsenthroughoutlife.Thepresenceofproteinintheurine(whichcausesfoamyurine)isoftenthefirstsignofkidneyinvolvement.End-stagekidneyfailureinthosewithFabrydiseasetypicallyoccursinthethirddecadeoflife,andisacommoncauseofdeathduetothedisease.[citationneeded] Heart[edit] Fabrydiseasecanaffecttheheartinseveralways.Theaccumulationofsphingolipidswithinheartmusclecellscausesabnormalthickeningoftheheartmuscleorhypertrophy.Thishypertrophycancausetheheartmuscletobecomeabnormallystiffandunabletorelax,leadingtoarestrictivecardiomyopathycausingshortnessofbreath.[7][8] Fabrydiseasecanalsoaffectthewayinwhichtheheartconductselectricalimpulses,leadingtobothabnormallyslowheartrhythmssuchascompleteheartblock,andabnormallyrapidheartrhythmssuchasventriculartachycardia.Theseabnormalheartrhythmscancauseblackouts,palpitations,orevensuddencardiacdeath.[7][8] Sphingolipidscanalsobuildupwithintheheartvalves,thickeningthevalvesandaffectingthewaytheyopenandclose.Ifsevere,thiscancausethevalvestoleak(regurgitation)ortorestricttheforwardflowofblood(stenosis).Theaorticandmitralvalvesaremorecommonlyaffectedthanthevalvesontherightsideoftheheart.[7][8] Skin[edit] Angiokeratomas(tiny,painlesspapulesthatcanappearonanyregionofthebody,butarepredominantonthethighs,aroundthenavel,buttocks,lowerabdomen,andgroin)arecommon.[9] Anhidrosis(lackofsweating)isacommonsymptom,andlesscommonlyhyperhidrosis(excessivesweating).[citationneeded] Additionally,patientscanexhibitRaynaud'sdisease-likesymptomswithneuropathy(inparticular,burningextremitypain).[citationneeded] Ocularinvolvementmaybepresentshowingcorneaverticillata(alsoknownasvortexkeratopathy),i.e.cloudingofthecorneas.Keratopathymaybethepresentingfeatureinasymptomaticpatients,andmustbedifferentiatedfromothercausesofvortexkeratopathy(e.g.drugdepositioninthecornea).[10]Thiscloudingdoesnotaffectvision.[10] Otherocularfindingscanincludeconjunctivalandretinalvascularabnormalitiesandanterior/posteriorspoke-likecataract.Visualreductionfromthesemanifestationsisuncommon.[citationneeded] Othermanifestations[edit] Fatigue,neuropathy(inparticular,burningextremitypain,redhandsandfeetonandoff),cerebrovasculareffectsleadingtoanincreasedriskofstroke-earlystrokes,mostlyvertebrobasilarsystemtinnitus(ringingintheears),vertigo,nausea,inabilitytogainweight,chemicalimbalances,anddiarrheaareothercommonsymptoms.[citationneeded] Causes[edit] FabrydiseaseiscausedbyaDNAsequence(gene)thatisnotfunctioningasitshould.Apersonwhoinheritsthisgenedoesnothaveenoughofafunctioningenzymeknownasalpha-galactosidaseA.Thelackofalpha-galactosidaseleadstoFabrydisease.AdeficiencyofalphagalactosidaseA(a-GALA,encodedbyGLA)duetomutationcausesaglycolipidknownasglobotriaosylceramide(abbreviatedasGb3,GL-3,orceramidetrihexoside)toaccumulatewithinthebloodvessels,othertissues,andorgans.[11]Thisaccumulationleadstoanimpairmentoftheirproperfunctions.[citationneeded] Atleast443disease-causingmutationsintheGLAgenehavebeendiscovered.[12]TheDNAmutationsthatcausethediseaseareX-linkedrecessivewithincompletepenetranceinheterozygousfemales.Theconditionaffectshemizygousmales(i.e.allnon-intersexmales),aswellashomozygous,andinmanycasesheterozygousfemales.Whilemalestypicallyexperienceseveresymptoms,womencanrangefrombeingasymptomatictohavingseveresymptoms.Researchsuggestsmanywomenexperienceseveresymptomsrangingfromearlycataractsorstrokestohypertrophicleftventricularheartproblemsandkidneyfailure.ThisvariabilityisthoughttobeduetoX-inactivationpatternsduringembryonicdevelopmentofthefemale.[13] Mechanism[edit] Fabrydiseaseisaninheritedlysosomalstoragedisorderthatiscausedbyadeficiencyofalpha-galactosidaseA.Thisenzymedeficiencyisaresultofanaccumulationofglycosphingolipidsfoundinthelysosomesandmostcelltypesandtissues,whichleadsittobeconsideredamultisystemdisease.Indicationsincludepainfulcrisis,angiokeratomas,cornealdystrophy,andhypohydrosis.[14]Inseverecasesthereisrenal,cerebrovascular,andcardiacinvolvementanditispredominatelyresponsibleforprematuremortalityinFabrypatients.[14]FabrydiseaseisX-linkedandmanifestsmostlyinhomozygousmalesbutalsoinheterozygousfemales.CardiacinvolvementisrecurrentinFabrypatients.Patientshavedevelopedhypertrophiccardiomyopathy,arrhythmias,conductionabnormalities,andvalvularabnormalities.[14]Deficientactivityoflysosomalalpha-galactosidaseresultsinprogressiveaccumulationofglobotriaosylceramide(GL-3)withinlysosomes,thatisbelievedtotriggeracascadeofcellularevents.[15]Thedemonstrationofmarkedalpha-galactosidasedeficiencyistheconclusivemethodforthediagnosisinhomozygousmales.Itmaybedetectedinheterozygotousfemales,butitisofteninconclusiveduetorandomX-chromosomalinactivation,somoleculartesting(genotyping)offemalesismandatory.[15] Diagnosis[edit] Fabrydiseaseissuspectedbasedontheindividual'sclinicalpresentation,andcanbediagnosedbyanenzymeassay(usuallydoneonleukocytes)tomeasurethelevelofalpha-galactosidaseactivity.AnenzymeassayisnotreliableforthediagnosisofdiseaseinfemalesduetotherandomnatureofX-inactivation.MoleculargeneticanalysisoftheGLAgeneisthemostaccuratemethodofdiagnosisinfemales,particularlyifthemutationshavealreadybeenidentifiedinmalefamilymembers.Manydisease-causingmutationshavebeennoted.KidneybiopsymayalsobesuggestiveofFabrydiseaseifexcessivelipidbuildupisnoted.Pediatricians,aswellasinternists,commonlymisdiagnoseFabrydisease.[16]Allimmediateandextendedfamilymembersinthesamefamilyhavethesamefamilymutation,soifonememberofafamilyhasaDNAsequenceanalysisperformed,othermembersofthefamilycanbediagnosedbyperformingatargetedsequenceanalysisinsteadoftestingtheentiregene.[17]Targetedsequencingisquickerandlessexpensivetoperform.Onestudyreportedthatforeveryfirstdiagnosisinafamily,onaveragefivemorefamilymembers(immediateandextended)arealsodiagnosed.[17] MRIisaccurateinaccessingleftventricularmassandthicknessandhypertrophy.Lategadoliniumenhancementshowsincreasedsignalofthemidwallattheinferolateralwallofthebaseoftheleftventricle,usuallyinthenon-hypertrophicventricle.T1-weightedimagingcanshowlowT1signalduetosphingolipidstorageintheheartevenwithoutventricularhypertrophyin40%ofthethoseaffectedbythedisease.Thus,MRIisausefulwayofdiagnosingthediseaseearly.[18]T2signalisincreasedininflammationandoedema.[19] Treatment[edit] ThetreatmentsavailableforFabrydiseasecanbedividedintotherapiesthataimtocorrecttheunderlyingproblemofdecreasedactivityofthealphagalactosidaseAenzymeandtherebyreducetheriskoforgandamage,andtherapiestoimprovesymptomsandlifeexpectancyonceorgandamagehasalreadyoccurred.[citationneeded] Therapiestargetingenzymeactivity[edit] Enzymereplacementtherapyisdesignedtoprovidetheenzymethepatientismissingasaresultofageneticmalfunction.Thistreatmentisnotacure,butcanpartiallypreventdiseaseprogression,andpotentiallyreversesomesymptoms.[20]AsofMarch 2022[update],twomedicaldrugsbasedonenzymereplacementtherapyareavailableforFabrydisease: Agalsidasealfa,soldunderthebrandnameReplagalbythecompanyTakeda(sinceitsacquisitionofthecompanyShire),isarecombinantformofalpha-galactosidase A[21]ItreceivedapprovalintheEUin2001.[22]FDAapprovalwasappliedfortheUnitedStates.[23]However,ShirewithdrewtheirapplicationforapprovalintheUnitedStatesin2012,citingthattheagencywillrequireadditionalclinicaltrialsbeforeapproval.[24]AsofMarch 2022[update],ReplagalhasnotreceivedFDAapproval.[25] Agalsidasebeta,soldunderthebrandnameFabrazymebythecompanySanofiGenzyme,isanotherrecombinantformofalpha-galactosidase.Likereplagal,itreceivedapprovalintheEUin2001.[26]In2003,itwasthefirsttreatmentforFabrydiseasetobeapprovedbytheFDA.[27] Clinically,thetwotreatmentsaregenerallysimilarineffectivenessandsafety,[28]howevertheyhaveneverbeencompareddirectlyinarandomizedtrial.[29]Botharegivenbyintravenousinfusioneverytwoweeks.[22][26]TheyareavailableinEuropeandinmanyotherpartsoftheworld,buttreatmentcostsremainveryhigh.[30] Pharmacologicalchaperonetherapyisanotherstrategytomaintainenzymeactivity.Itdoessobyassistingcorrectfoldingofalpha-galactosidasedespitethemutationsthatcauseFabrydisease.AsofMarch 2022[update],onemedicaldrugbasedonpharmacologicalchaperonetherapyisavailableforFabrydisease: Migalastat,soldunderthebrandnameGalafoldbythecompanyAmicusTherapeutics,isapharmacologicalchaperonethatcanstabilizemanymutantformsofalpha-galactosidase.Itistakenbymouth.InarandomizedtrialcomparingMigalastatwithenzymereplacementtherapy,theefficacyandsafetyofbothtreatmentsweresimilar.[31][32]TheUSFoodandDrugAdministration(FDA)grantedGalafoldorphandrugstatusin2004,[33]andtheEuropeanCommissionfollowedin2006.[34]TheEuropeanMedicinesAgency'sCommitteeforMedicinalProductsforHumanUse(CHMP)grantedthedrugamarketingapprovalunderthenameGalafoldinMay2016.[35][36][37]FDAapprovalfollowedin2018.[38] ExperimentaltherapiesthatarecurrentlynotapprovedfortreatmentasofMarch 2022[update]includethefollowing: Agenetherapytreatmentthatisinearly-phaseclinicaltrials,[39][40]withthetechnologylicensedtoAvroBio.[41] Plant-basedERT(pegunigalsidasealfa)underdevelopmentbythecompanyProtalix ThesubstratereductiontherapyVenglustat(Ibiglustat)underdevelopmentbySanofi-Genzyme[42] Bio-betterERT(CDX-6311)underpre-clinicaldevelopmentbythecompanyCodexis Agenetherapy(ST-920)underdevelopmentbythecompanySangamo.[43] Organ-specifictreatment[edit] PainassociatedwithFabrydiseasemaybepartiallyalleviatedbyenzymereplacementtherapyinsomepatients,butpainmanagementregimensmayalsoincludeanalgesics,anticonvulsants,andnonsteroidalanti-inflammatorydrugs,thoughthelatterareusuallybestavoidedinkidneydisease.ThekidneyfailureseeninsomeofthosewithFabrydiseasesometimesrequireshaemodialysis.ThecardiaccomplicationsofFabrydiseaseincludeabnormalheartrhythms,whichmayrequireapacemakerorimplantablecardioverter-defibrillator,whiletherestrictivecardiomyopathyoftenseenmayrequirediuretics.[20] Prognosis[edit] LifeexpectancywithFabrydiseaseformaleswas58.2years,comparedwith74.7yearsinthegeneralpopulation,andforfemales75.4yearscomparedwith80.0yearsinthegeneralpopulation,accordingtoregistrydatafrom2001to2008.Themostcommoncauseofdeathwascardiovasculardisease,andmostofthosehadreceivedkidneyreplacements.[44] Epidemiology[edit] Fabrydiseaseispanethnic,butduetoitsrarity,determininganaccuratediseasefrequencyisdifficult.[15]Reportedincidences,rangingfromonein476,000toonein117,000inthegeneralpopulation,maylargelyunderestimatethetrueprevalence.[15]Newbornscreeninginitiativeshavefoundanunexpectedlyhighprevalenceofthedisease,ashighasoneinabout3,100newbornsinItalyandhaveidentifiedasurprisinglyhighfrequencyofnewbornmalesaroundonein1,500inTaiwan.[15] Research[edit] Enzymereplacementtherapy:Replacementofthemissingenzymetoclearthelipids(GL-3)fromthecells[17] Substratesynthesisinhibition,alsocalledsubstratereductiontherapy:Inhibitstheproductionofthelipid(GL-3)thataccumulatesinthecells[17] Chaperonetherapy:Usessmall-moleculedrugsthatbindtothedefectiveenzymeandstabilizeittoincreaseenzymeactivityandincreasecellularfunction[17] Geneediting:Technologythatcanpotentiallycutandfixabrokengeneinacell[17] Genetherapy:Geneticallymodifiestheaffectedcellstoproducethemissingenzyme.[17] History[edit] FabrydiseasewasfirstdescribedbydermatologistJohannesFabry[2]andsurgeonWilliamAnderson[3]independentlyin1898.[4]Itwasrecognisedtobeduetoabnormalstorageoflipidsin1952.Inthe1960s,theinheritancepatternwasestablishedasbeingX-linked,aswellasthemoleculardefectresponsibleforcausingtheaccumulationofglycolipids.[4] KenHashimotopublishedhisclassicpaperonhiselectronmicroscopicfindingsinFabrydiseasein1965.[45][46] ThefirstspecifictreatmentforFabrydiseasewasapprovedin2001.[20][47] Societyandculture[edit] House("EpicFail",seasonsix,episodethree)centersonapatientwithFabrydisease. Scrubs("MyCatalyst",seasonthree,episode12)featuresaFabrydiseasediagnosis. CrossingJordan("There'sNoPlaceLikeHome",seasontwo,episodeone)featuresapatientwhodiedfromFabrydisease. TheVillage(Koreandrama):"Achiara'sSecret"[48]featuresdaughtersofaserialrapistwhofindeachotherbecausetheyshareFabrydisease. DoctorJohn(Koreandrama):Inepisodetwo,aprisonerisdiagnosedwithFabrydisease. InLincolnRhyme:HuntfortheBoneCollector,acopycatofthetitularBoneCollectorhasFabrydiseaseandtakesGalafold,whichallowsthedetectivestolearnhisidentity. PartnersforJustice2(Koreandrama),featuresDoctorK,whohadFabrydisease. Doc(Italiandrama):SeriestwofeaturesanepisodewithatennisplayerwhoisdiagnosedwithFabrydisease Seealso[edit] Migalastat References[edit] ^James,Berger&Elston2006,p. 538 ^abFabry,Joh(December1898)."EinBeitragzurKenntnissderPurpurahaemorrhagicanodularis(PurpurapapulosahaemorrhagicaHebrae)"[Acontributiontotheknowledgeofthepurpurahaemorrhagicanodularis(purpurapapulosahaemorrhagicaHebrae)].ArchivfürDermatologieundSyphilis(inGerman).43(1):187–200.doi:10.1007/bf01986897.S2CID 33956139. ^abAnderson,William(April1898)."ACaseof'Angeio-Keratoma'".BritishJournalofDermatology.10(4):113–117.doi:10.1111/j.1365-2133.1898.tb16317.x.S2CID 70966125. ^abcSchiffmann,Raphael(2015)."Fabrydisease".NeurocutaneousSyndromes.HandbookofClinicalNeurology.Vol. 132.pp. 231–248.doi:10.1016/B978-0-444-62702-5.00017-2.ISBN 9780444627025.PMID 26564084. ^"Fabrydisease|GeneticandRareDiseasesInformationCenter(GARD)–anNCATSProgram".rarediseases.info.nih.gov.Retrieved2018-04-17. 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^abcPerrot,Andreas;Osterziel,KarlJosef;Beck,Michael;Dietz,Rainer;Kampmann,Christoph(1November2002)."FabryDisease:FocusonCardiacManifestationsandMolecularMechanisms".Herz.27(7):699–702.doi:10.1007/s00059-002-2429-9.PMID 12439642.S2CID 25962218. ^abcdeGermain,DominiqueP(2010)."Fabrydisease".OrphanetJournalofRareDiseases.5(1):30.doi:10.1186/1750-1172-5-30.PMC 3009617.PMID 21092187. ^Marchesoni,CintiaL.;Roa,Norma;Pardal,AnaMaría;Neumann,Pablo;Cáceres,Guillermo;Martínez,Pablo;Kisinovsky,Isaac;Bianchi,Silvia;Tarabuso,AnaLía;Reisin,RicardoC.(May2010)."MisdiagnosisinFabrydisease".TheJournalofPediatrics.156(5):828–31.doi:10.1016/j.jpeds.2010.02.012.PMID 20385321. ^abcdefg"Youarebeingredirected..."www.fabrydisease.org.Retrieved2019-12-13. ^Hagège,Albert;Réant,Patricia;Habib,Gilbert;Damy,Thibaud;Barone-Rochette,Gilles;Soulat,Gilles;Donal,Erwan;Germain,DominiqueP.(April2019)."Fabrydiseaseincardiologypractice:Literaturereviewandexpertpointofview".ArchivesofCardiovascularDiseases.112(4):278–287.doi:10.1016/j.acvd.2019.01.002.PMID 30826269. ^Baig,S;Vijapurapu,R;Alharbi,F;Nordin,S;Kozor,R;Moon,J;Bembi,B;Geberhiwot,T;Steeds,RP(2019-01-01)."DiagnosisandtreatmentofthecardiovascularconsequencesofFabrydisease".QJM:AnInternationalJournalofMedicine.112(1):3–9.doi:10.1093/qjmed/hcy120.ISSN 1460-2725.PMID 29878206. ^abcWanner,Christoph;Arad,Michael;Baron,Ralf;Burlina,Alessandro;Elliott,PerryM.;Feldt-Rasmussen,Ulla;Fomin,VictorV.;Germain,DominiqueP.;Hughes,DerralynnA.(June2018)."EuropeanexpertconsensusstatementontherapeuticgoalsinFabrydisease"(PDF).MolecularGeneticsandMetabolism.124(3):189–203.doi:10.1016/j.ymgme.2018.06.004.ISSN 1096-7206.PMID 30017653.S2CID 51676692. ^Keating,GillianM.(October2012)."Agalsidasealfa:areviewofitsuseinthemanagementofFabrydisease".BioDrugs.26(5):335–354.doi:10.2165/11209690-000000000-00000.PMID 22946754. ^ab"ReplagalEPAR".Retrieved2022-03-21. ^"WithALife-SavingMedicineInShortSupply,PatientsWantPatentBroken".NPR.org.2010-08-04.Archivedfromtheoriginalon14September2010.Retrieved2010-09-02. ^Grogan,K.(2012-03-15)."ShirewithdrawsReplagalinUSAasFDAwantsmoretrials".PharmaTimes.Archivedfromtheoriginalon2014-08-19. ^"ReplagalFDAApprovalStatus".Retrieved2022-03-21. ^ab"FabrazymeEPAR".Retrieved2022-03-21. ^"DrugApprovalPackage:FABRAZYME(AGALSIDASEBETA)".www.fda.gov.Retrieved2022-03-21. ^Arends,Maarten;Biegstraaten,Marieke;Wanner,Christoph;Sirrs,Sandra;Mehta,Atul;Elliott,PerryM.;Oder,Daniel;Watkinson,OliverT.;Bichet,DanielG.;Khan,Aneal;Iwanochko,Mark;Vaz,FrédéricM.;VanKuilenburg,AndréBP.;West,MichaelL.;Hughes,DerralynnA.;Hollak,CarlaEM.(2018)."AgalsidasealfaversusagalsidasebetaforthetreatmentofFabrydisease:Aninternationalcohortstudy".JournalofMedicalGenetics.55(5):351–358.doi:10.1136/jmedgenet-2017-104863.PMC 5931248.PMID 29437868. ^"SearchforinterventionaltrialswithReplagalandFabrazymeonclinicaltrials.gov".Retrieved2022-03-21. ^Turner,NeilN;Turner,NeilN;Lameire,Norbert;Goldsmith,DavidJ;Winearls,ChristopherG;Himmelfarb,Jonathan;Remuzzi,Giuseppe,eds.(2015).Fabrydisease:Managementandoutcome.Vol. 1.OxfordUniversityPress.doi:10.1093/med/9780199592548.003.0338.ISBN 9780199592548. ^Hughes,D.A.;et al.(2017)."OralpharmacologicalchaperonemigalastatcomparedwithenzymereplacementtherapyinFabrydisease:18-monthresultsfromtherandomisedphaseIIIATTRACTstudy".JournalofMedicalGenetics.54(4):288–296.doi:10.1136/jmedgenet-2016-104178.PMC 5502308.PMID 27834756. ^ClinicaltrialnumberNCT01218659for"StudytoComparetheEfficacyandSafetyofOralAT1001andEnzymeReplacementTherapyinPatientsWithFabryDisease"atClinicalTrials.gov ^"MigalastatOrphanDrugDesignationsandApprovals".U.S.FoodandDrugAdministration(FDA).Retrieved16September2020. ^"EU/3/06/368".EuropeanMedicinesAgency(EMA).Retrieved16September2020. ^"AmicusTherapeuticsAnnouncesEuropeanCommissionApprovalforGalafold(Migalastat)inPatientswithFabryDiseaseinEuropeanUnion".GlobeNewswire.31May2016. ^"SummaryofProductCharacteristicsforGalafold"(PDF).EuropeanMedicinesAgency.June2016. ^"GalafoldEPAR".EuropeanMedicinesAgency(EMA).Retrieved16September2020. ^"DrugApprovalPackage:Galafold(migalastat)".www.fda.gov.Retrieved2022-03-21. ^"CanadalaunchesfirstgenetherapytrialforFabrydisease".EurekAlert!.RetrievedMay31,2020. ^"Open-Label,StudyOfEfficacyandSafetyOfAVR-RD-01forTreatment-NaiveSubjectsWithClassicFabryDisease-FullTextView-ClinicalTrials.gov".clinicaltrials.gov.RetrievedMay31,2020. ^"UHNStart-upAVROBIO,Inc.Announces$60MillionSeriesBFinancingtoAdvanceGeneTherapyPipelineforLysosomalStorageDisordersandApplyLentiviralPlatformtoOtherGeneticDiseases|TDC". ^"Venglustat(Ibiglustat)".Retrieved2022-03-21. ^"FabryDiseaseTreatment".www.fabrydisease.org.Retrieved2022-03-21. ^Waldek,Stephen;Patel,ManeshR.;Banikazemi,Maryam;Lemay,Roberta;Lee,Philip(November2009)."LifeexpectancyandcauseofdeathinmalesandfemaleswithFabrydisease:findingsfromtheFabryRegistry".GeneticsinMedicine.11(11):790–796.doi:10.1097/GIM.0b013e3181bb05bb.PMID 19745746. ^JohnThorneCrissey;LawrenceC.Parish;KarlHolubar(2013).HistoricalAtlasofDermatologyandDermatologists.CRCPress.p. 179.ISBN 978-1-84214-100-7. ^Mehta,Atul;Beck,Michael;Linhart,Aleš;Sunder-Plassmann,Gere;Widmer,Urs(2006),Mehta,Atul;Beck,Michael;Sunder-Plassmann,Gere(eds.),"Historyoflysosomalstoragediseases:anoverview",FabryDisease:Perspectivesfrom5YearsofFOS,OxfordPharmaGenesis,ISBN 978-1903539033,PMID 21290707,retrieved10August2018 ^"ShireSubmitsBiologicsLicenseApplication(BLA)forReplagalwiththeU.S.FoodandDrugAdministration(FDA)".FierceBiotech. ^"TheVillage:Achiara'sSecret". Furtherreading[edit] James,WilliamD.;Berger,TimothyG.;Elston,Dirk(2006).Andrews'DiseasesoftheSkin:clinicalDermatology.SaundersElsevier.ISBN 978-0-7216-2921-6. Schiffmann,Raphael;Kopp,JeffreyB.;Austin,HowardA.;Sabnis,Sharda;Moore,DavidF.;Weibel,Thais;Balow,JamesE.;Brady,RoscoeO.(June2001)."EnzymereplacementtherapyinFabrydisease:arandomizedcontrolledtrial".JAMA.285(21):2743–2749.doi:10.1001/jama.285.21.2743.PMID 11386930. Wilcox,WilliamR.;Banikazemi,Maryam;Guffon,Nathalie;Waldek,Stephen;Lee,Philip;Linthorst,GaborE.;Desnick,RobertJ.;Germain,DominiqueP.(July2004)."Long-termsafetyandefficacyofenzymereplacementtherapyforFabrydisease".AmericanJournalofHumanGenetics.75(1):65–74.doi:10.1086/422366.PMC 1182009.PMID 15154115. Externallinks[edit] ClassificationDICD-10:E75.2(ILDSE75.25)ICD-9-CM:272.7OMIM:301500MeSH:D000795DiseasesDB:4638ExternalresourceseMedicine:neuro/579derm/707ped/2888GeneReviews:Fabrydisease FabryDiseaseInformationPageatNINDS FabrydiseaseatNLMGeneticsHomeReference Authoritycontrol:Nationallibraries Germany Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Fabry_disease&oldid=1096924867" Categories:X-linkedrecessivedisordersRarediseasesLipidstoragedisordersSkinconditionsresultingfromerrorsinmetabolismLysosomalstoragediseasesCardiogeneticdisordersHiddencategories:CS1German-languagesources(de)WikipediaarticlesneedingpagenumbercitationsfromSeptember2010ArticleswithshortdescriptionShortdescriptionmatchesWikidataShortdescriptionisdifferentfromWikidataAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromJuly2014ArticleswithunsourcedstatementsfromFebruary2021ArticlescontainingpotentiallydatedstatementsfromMarch2022AllarticlescontainingpotentiallydatedstatementsArticleswithGNDidentifiers Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommons Languages العربيةCatalàDeutschEestiEspañolفارسیFrançaisGalegoItalianoעבריתМакедонскиNederlands日本語PolskiPortuguêsРусскийSlovenščinaСрпски/srpskiSuomiSvenskaТатарча/tatarçaTürkçeاردو中文 Editlinks