A
Fordøjelsesorganer og stofskifte
Pompes sygdom
Pompes sygdom forårsages af en autosomal recessiv arvelig mangel på det lysosomale enzym, sur α-glukosidase. Mangel på enzymet medfører ophobning intralysosomalt af glycogen i mange væv, især hjerte- og skeletmuskulatur, herunder respirationsmuskulatur.
Kliniske manifestationer er progressive og inkluderer hypertrofisk kardiomyopati og muskelsvækkelse, herunder respirationsinsufficiens. Der er tale om et klinisk kontinuum med svær og hurtigt progredierende sygdom ved debut før 6-måneders-alderen (infantile type) og mere protraherede forløb hos større børn og voksne.
Kardiomyopati ses primært hos spædbørn med den infantile type, men er sjælden i andre aldersgrupper, hvor påvirkning af skeletmuskulatur dominerer.
Diagnostik
Diagnosen stilles ved måling af aktiviteten af sur α-glukosidase i lymfocytter med efterfølgende molekylærgenetisk analyse.
Behandlingsvejledning
Effekten af enzymsubstitutionsbehandling med alglucosidase-alfa er veldokumenteret hos patienter med infantil type vurderet på forbedret overlevelse og motorik samt reduktion i anvendelsen af respirationsunderstøttende behandling. Visse patienter med svær sygdom (inkl. CRIM negativ sygdom) har brug for immunmodulerende behandling og ERT i øget dosis fra behandlingsstart. Der er ligeledes overbevisende effekt på senere debuterende typer hos nogle patienter, særligt i forhold til mobilitet. For alle typer er effekten individuelt varierende. Tidlig iværksættelse af behandlingen er essentiel for opnåelsen af det bedste resultat, men andre faktorer, herunder det immunologiske respons, ernærings- og træningsmæssige forhold spiller også ind.
Behandlingen er en specialistopgave og bør forestås af læger med særligt kendskab til Pompes sygdom.
Revurdering af behandling
En revurdering af behandlingsindikation er særligt vigtig efter start af behandling i et fremskredent stadium af sygdommen, herunder særligt i forhold til motorisk og respiratorisk funktion samt CRIM-status, hvor effekt af behandling kan være beskeden, og en løbende vurdering af behov for dosisjustering, skift af behandling samt den kliniske meningsfuldhed er vigtig.
Referencer
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