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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Prof. Dr. Bernhard Kunath
Klinik und Poliklinik für Neurologie der Medizinischen Fakultät der TU Dresden
Fetscherstraße 74
01307 Dresden