Morbus Fabry

Zusammenfassung

Die Morbus Fabry Erkrankung ist eine seltene, X-chromosomal vererbbare, lysosomale Speichererkrankung, bedingt durch eine Mutation im α-Galaktosidase-A-Gen (GLA). Bei betroffenen Patienten kommt es dadurch zu einem Mangel des lysosomalen Enzyms α-Galaktosidase A, welches unter normaler Konzentration beim Abbauprozess von zellmembranständigem Globotriaosyceramid (Gb3) beteiligt ist. Dieser Enzymmangel führt zur sukzessiven Akkumulation von Gb3 in zahlreichen Organen. Die Folge ist eine nachhaltige Parenchym- und Funktionsschädigung der betroffenen Organsysteme.

Das Spektrum klinischer Symptome ist vielfältig und reicht von den im Kindes- und Jugendalter oft diagnostizierten Akroparästhesien, Hypohidrosis, Angiokeratomen und Hornhauttrübungen bis hin zu schweren pathologischen Veränderungen in Nieren, Herz, ZNS sowie anderen Organen im Erwachsenenalter. Morbus Fabry Patienten leiden unter einer erhöhten Morbidität und Mortalität, und haben unbehandelt eine verminderte Lebenserwartung (Männer ca. 20 Jahre, Frauen ca. 15 Jahre). Der klinische Phänotyp ist sehr variabel: während Männer unbehandelt im Verlauf meistens schwer erkranken, treten die Symptome bei Frauen zeitlich verzögert und milder auf. Aufgrund der mutationsbedingt individuellen Krankheitsverläufe wird die Diagnose in erster Linie aufgrund der klinischen Symptome gestellt und durch einen laborchemischen Nachweis einer verminderten α-Galaktosidase-A-Aktivität im Blut sowie durch eine genetische Mutationsanalyse gesichert. Neben einer symptomorientierten, konservativen Therapie ist durch die Einführung der Enzymersatztherapie (EET) seit 2001 eine kausale Behandlung des M. Fabry möglich. Nach heutigen Erkenntnissen bewirkt die EET eine Stabilisierung bzw. zum Teil sogar eine Verbesserung von Symptomen und Lebensqualität und hat zugleich das Potenzial, die Mortalität zu verringern. Um Organschäden zu verhindern bzw. zu mildern, ist eine frühe Diagnose und Behandlung erstrebenswert.

Abstract

Fabry disease is an inherited X-linked lysosomal storage disease due to a genetic defect of the GLA gene which encodes the protein of the enzyme α-galaktosidase A. Under normal concentrations this lysosomal enzyme is involved in degradation and catabolism processes of membrane glycosphingolipids in almost all cells of the human organism. The enzyme deficiency leads to a progessive accumulation of globotriaosylceramide (Gb3) in various tissues and organ systems and is responsible for the large variability of the clinical signs and symptoms of the disease.

First signs and symptoms such as painful neuropathy (acroparethesia), hypo- or unhidrosis and gastrointestinal disturbances can be found already in childhood and mainly affect quality of life. In the following decades of life, renal cardiac, and cerebrovascular complications occur in hemizygous males and with some delay in a part of heterozygous females as well. If not treated, these complications result in increased morbidity and premature mortality.

With the introduction of the enzyme replacement therapy (ERT) in 2001 a causal treatment is available. Published data from clinical trials and observational studies demonstrated that ERT mitigates signs and symptoms of the disease as well as quality of life, and has the potential to reduce mortality. The efficacy of ERT seems to be less pronounced in severe cases of the disease, which makes an early diagnosis and treatment more important in order to prevent or improve the progression of the disease.

Schlüsselwörter

Morbus Fabry - α-Galaktosidase A - Glykosphingolipide

Key words

Fabry disease - α-galactosidase A - glycosphingolipids

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