Morbus Fabry – Komplexe Klinik, einfache Diagnostik, kausale Therapie

Zusammenfassung

Der Morbus Fabry ist eine angeborene Stoffwechselkrankheit aus der Gruppe der lysosomalen Speicherkrankheiten. Ursächlich liegt der Erkrankung ein Mangel des Enzyms α-Galaktosidase A zu Grunde. Folge ist die Akkumulation von Globotriaosylceramid in nahezu allen Zellen des Körpers. Aufgrund einer progredienten Schädigung einer Vielzahl von Organen resultiert ein Funktionsverlust betroffener Organe. Angiokeratome, Akroparästhesien, Proteinurie, Hornhauttrübung und gastrointestinale Beschwerden manifestieren sich häufig bereits in der Kindheit. Mit zunehmendem Alter treten kardiale (Kardiomyopathie), renale (progrediente Niereninsuffizienz) und zentralnervöse Manifestationen (TIA/Apoplex) stärker in den Vordergrund. Unbehandelt sterben die Betroffenen mit ca. 55 (Männer) bzw. 70 Jahren (Frauen). Seit 2001 existiert eine kausale Behandlungsmöglichkeit für den M. Fabry in Form der Enzymersatztherapie. Die Prognose der Patienten dürfte damit entscheidend von einer frühzeitigen Diagnose und Therapie abhängen. Immer noch beträgt aber die Zeitspanne zwischen dem Auftreten erster Symptome und der Diagnosestellung durchschnittlich 13 Jahre. Mit der vorliegenden Arbeit wird das variable klinische Bild des M. Fabry übersichtsartig zusammengestellt, und es wird eine Anleitung zur rationalen Diagnose und Therapie des M. Fabry gegeben.

Abstract

Fabry disease is an inherited metabolic disease, and one of several lysosomal storage diseases. Basis of the disease is the deficiency of α-galactosidase A. Consequence of this deficiency is the accumulation of globotriaosylceramide in virtually all cells of the body. Affected organs cannot fulfil their function but will be progressively damaged. Often, angiokeratoma, acroparaesthesia, proteinuria, corneal clouding and gastrointestinal complaints become manifest in childhood already. With age, cardiac (cardiomyopathy), renal (progressive renal insufficiency) and central-nervous manifestations (TIA/stroke) come to the fore. Untreated patients die at the age of approximately 55 years (males) and 70 years (Frauen), respectively. Since 2001 a causal treatment for Fabry disease is available in the form of enzyme replacement therapy. By then, prognosis may primarily depend on an early diagnosis and timely therapy. Nevertheless, the mean time between onset of symptoms and diagnosis has been reported to be 13 years. The present report reviews the variable clinical manifestations of Fabry disease, and offers rationale guidance for diagnosis and therapy.

Schlüsselwörter

lysosomale Speicherkrankheit - Enzymersatztherapie - Globotriaosylceramid/Gb3 - α-Galaktosidase A - GLA-Gen

Key words

lysosomal storage disease - enzyme replacement therapy - globotriaosylceramide/Gb3 - α-galactosidase A - GLA-Gene

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