Diagnostik und Therapie der Homocystinurie

Zusammenfassung

Die Homocystinurie ist eine seltene angeborene Erkrankung des Methioninstoffwechsels, die mit einer pathologischen Erhöhung der nicht proteinogenen Aminosäure Homocystein und der Ausscheidung ihres Disulfids Homocystin über den Urin einhergeht. Mehrere biochemische und genetische Defekte können zu einer deutlichen Homocysteinerhö-hung führen, darunter Störungen des Vita-min-B₆-, Folsäure- und Vitamin-B₁₂-Stoffwechsels, sodass der Terminus Homocystinurie eine Erkrankungsgruppe zusammenfasst. Die häufigste Ursache der Homocystinurie, auch klassische Homocystinurie oder Homo-cystinurie Typ I genannt, stellt die hereditäre Cystathionin-β-Synthase-Defizienz dar, die mit einer Erhöhung von Homocystein und Methionin im Blut einhergeht. Die Diagnose wird durch Bestimmung von Homocystein im Plasma gestellt und kann biochemisch und genetisch gesichert werden. Unbehandelt zeigen sich eine erhebliche Morbidität und Mortalität, die durch Ausschöpfung der therapeutischen Optionen, bestehend aus Vitamin B₆, Folsäure, Vitamin B₁₂, Betain und einer Proteinrestriktion mit Aminosäuresupplementie-rung, erheblich reduziert werden können.

Summary

Homocystinuria is a rare inherited disease affecting the metabolism of methionine, associated with a pathological elevation of the nonproteinogenic amino acid homocysteine and the secretion of the disulfide homocystine in the urine. Several biochemical and genetic disorders can lead to a distinct elevation of homocysteine including disorders affecting vitamin B₆, vitamin B₁₂ and tetrahydrofolate metabolism. The main cause, the cystathionin ß-synthase-deficiency is associated with increased homocysteine and methionine blood levels. The determination of elevated homo-cysteine levels in the blood is the main diagnostic tool for any variant of homocystinuria, biochemical and genetic analysis confirm the diagnosis. Untreated patients show high morbidity and mortality, which can be ameliorated by a therapy consisting of pyridoxine, folic acid, betaine and a dietary protein restriction with amino acid supplementation.

Schlüsselwörter

Homocystinurie - Methioninstoffwechsel - Homocystein

Keywords

Homocystinuria - methionine metabolism - homocysteine

• Literatur

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