Das klinische Spektrum von Harnstoffzyklusdefekten im Erwachsenenalter

Zusammenfassung

Harnstoffzyklusdefekte gehören zu den häufigsten Stoffwechselkrankheiten mit einer kumulativen Inzidenz von 1:8000. Gemeinsames Merkmal ist die gestörte Detoxifikation von Ammoniak mit konsekutiver Hyperammonämie bei Stickstoffbelastung. Die Patienten werden meist bereits im Säuglings- oder Kleinkindalter mit Erbrechen, zerebralen Krampfanfällen und Vigilanzminderung symptomatisch. Je nach betroffenem Enzym und seiner Restaktivität unterscheiden sich die Patienten im Alter bei Erstmanifestation, Art und Ausprägung der Symptome und in ihrer Anfälligkeit für metabolische Entgleisungen. Der Nachweis einer Hyperammonämie und die Analyse des Aminosäureprofils im Plasma geben die entscheidenden diagnostischen Hinweise. Aufgrund der durch moderne Therapiemodalitäten steigenden Lebenserwartung und der Möglichkeit einer Manifestation im Erwachsenenalter fallen diese Erkrankungen zunehmend in das Aufgabengebiet der Inneren Medizin. Die berichteten Fälle illustrieren den heterogenen klinischen Verlauf dieser Erkrankungen von der Kindheit bis zum Erwachsenenalter.

Abstract

Urea cycle defects belong to the most common metabolic disorders with a cumulative incidence of 1:8000. A common trait of urea cycle defects is a disturbed detoxification of ammonia leading to hyperammonemia in the event of a high nitrogen load. Most patients develop symptoms in the neonatal period or in infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the affected enzyme and its residual activity, patients differ in the age at first presentation, the character and severity of symptoms and in the susceptibility to metabolic derangement. The presence of hyperammonemia and an altered plasma amino acid profile give the essential diagnostic clues. Since modern therapeutic measures have prolonged the life expectancy of these patients and provided the possibility of a first presentation in adulthood, patients with urea cycle defects have become an increasing challenge in internal medicine. The reported case series illustrates the heterogeneous clinical course of these disorders from childhood to adulthood.

Schlüsselwörter

Harnstoffzyklusdefekte - Hyperammonämie - Glutaminsynthetase - Ornithintranscarbamylasemangel - Citrullinämie - Argininosuccinatlyasemangel

Key words

urea cycle defects - hyperammonaemia - glutamine synthetase - ornithine transcarbamylase deficit - citrullinaemia - argininosuccinate lyase deficit

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