Diagnostik und Therapie bei Morbus Wilson

Zusammenfassung

Der Morbus Wilson ist eine hereditäre autosomal-rezessive Erkrankung des Kupferstoffwechsels. Mehr als 200 verschiedene Mutationen am Genort, der die kupfertransportierende ATP-Pase 7B kodiert (13q14,3), verursachen die Erkrankung. Lebersymptomatik tritt meist während der ersten, neurologische und psychiatrische Symptomatik in der zweiten oder dritten Lebensdekade, selten später, auf. Genotyp-Phänotyp-Korrelationen sind wahrscheinlich. Die Diagnostik umfasst Laboratoriumsuntersuchungen (Kupfermetabolismus), Molekulargenetik und - wenn notwendig - die Leberbiopsie. Die Behandlung muss lebenslang fortgeführt werden, ohne Unterbrechung, selbst während der Schwangerschaft. Neben D-Penicillamin, das das Mittel der ersten Wahl für viele Jahre darstellte, werden Trientine, Zink und Tetrathiomolybdat mit gutem Erfolg eingesetzt. Therapieüberwachung (Kupferbilanz, Nebenwirkungen) - zumindest ein- oder zweimal jährlich - ist notwendig. Zerebrale MRT- und FDG-PET-Untersuchungen sind von praktischem Nutzen für die Überwachung der Langzeittherapie. Die kontinuierliche Betreuung von Wilson-Patienten (38, davon 10 asymptomatisch) in einer Spezialambulanz hat sich seit 1964 bewährt. 31 Patienten, konsequent mit D-Penicillamin behandelt, hatten kaum Nebenwirkungen. Selbst schwere neurologische Symptomatik besserte sich, einige Patienten wurden symptomfrei. Alle asymptomatischen Patienten blieben asymptomatisch. Trientine und Zink stellten bei D-Penicillamin-Unverträglichkeit eine effektive alternative Therapie dar. Wiederholt traten bei zwei Patientinnen Leberdekompensationen auf, bei einer wurde eine Lebertransplantation erforderlich. 19 Schwangerschaften konnten unbeeinträchtigt ausgetragen werden, fetale Schädigungen traten nicht auf (17 behandelt mit D-Penicillamin, 2 mit Trientine und Zink). Unterbrechung der Therapie führte zu einem tödlichen Leberversagen bei einer Schwangeren.

Abstract

Wilson's disease, an hereditary autosomal recessive disorder, is caused by more than 200 different mutations in the gene (locus 13q14,3), encodes a copper-transporting ATPase 7B. Hepatic manifestations became apparent mainly during the first, neurological and psychiatric during the second or third decade of life, seldom later. Genotype-phaenotype correlations are probably. The diagnosis involves laboratory tests (Cu-metabolism), molecular genetics and, if necessary, liver biopsy. Treatment must be continued lifelong, without disruption, also in the pregnancy. Besides D-Penicillamin, which has been the drug of choice for many years, Trientine, zinc and tetrathiomolybdate are used with good success. Monitoring (copper balance, side effects) - at least once or twice yearly - is necessary. Cerebral MRI and FDG-PET seems to be a useful tool in practise for long-term therapy. Continuous care of Wilson patients (38, 10 of among them without hepatic or neurological signs) in a specialised outpatients clinic since 1964 has proven worth. 31 patients consistently treated with D-Penicillamin tolerated the drug well with few side effects. Even marked neurological symptoms improved, some patients became virtually free of symptoms. All patients without clinical signs remained free of symptoms. If intolerance to D-Penicillamin occurs, Trientine and zinc are an effective alternative therapy. Recurrent hepatic decompensations were observed in 2 female patients. One of them eventually required a liver transplant. 19 pregnancies could be carried to full term without complications or fetal damage while taking medication (17 with D-Penicillamin, 2 with Trientine and zinc). Discontinuation of therapy resulted in fatal hepatic failure in one pregnant patient.

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