Zusammenfassung
Der Morbus Wilson, eine autosomal-rezessive Erkrankung des Kupferstoffwechsels, ist
durch eine variable klinische Konstellation von hepatischen, neurologischen und psychiatrischen
Leitsymptomen gekennzeichnet. Gegenwärtig sind ca. 250 verschiedene Mutationen des
ATP 7B-Genes bekannt, die als krankheitsauslösend gelten. Gegenstand der Diskussion
ist es, ob eine Genotyp-Phänotyp-Korrelation bezüglich dieser Mutationen vorliegt.
Die vorliegende Studie untersucht diese Frage bei 39 Patienten anhand der Genotypeinteilung
in homozygot (Gruppe I) bzw. compound heterozygot für die Mutation H1069Q (Gruppe
II) und anderer Mutationen (Gruppe III). Betrachtet werden der klinische Verlaufstyp,
der neurologische Schweregrad, epidemiologische Aspekte, das Vorliegen einer psychopathologischen
Störung, zentrale Latenzen der akustisch evozierten Potenziale (FAEP mit Welle III
und Interpeaklatenz III-V) und Befunde des kranialen MRT. Während die psychopathologischen
Befunde, Ergebnisse der FAEP und des MRT mit dem klinischen Verlaufstyp korrelieren,
lässt sich eine Genotyp-Phänotyp-Korrelation zum Vorliegen der H1069Q-Mutation nicht
nachweisen. Das qualitative und quantitative Befundmuster ist ohne signifikante Unterschiede
in den vorliegenden 3 Genotypgruppen. Entscheidende Bedeutung für die Ausprägung der
Befunde und ihre Reversibilität kommt weiterhin dem Zeitpunkt des Therapiebeginns
zur Begrenzung des toxischen Kupfereinflusses zu.
Abstract
Wilson's disease, a rare autosomal recessive disorder of hepatic copper transport,
is characterized by a varying pattern of hepatic, neurologic and psychiatric symptoms.
Currently, about 250 causative mutations of the ATP 7B gene are known. However, a
correlation between genotype and phenotype according to these mutations is not yet
clear. To elucidate a possible correlation in this study 39 patients with Wilson's
disease were subdivided into three groups according to the underlying mutation in
group I for homocygote respectively group II for compound heterocygote mutation in
H1069Q and group III for other mutations. Clinical subtype and extent of neurologic
disturbance as well as epidemiologic aspects, presence of psychiatric symptoms, results
of acustically evoked potentials (Wave III, interpeak latency III-V) and findings
of cranial MRI were considered. While psychopathological symptoms, the results of acustically evoked potentials and
cranial MRI show a correlation to the clinical subtype of Wilson's disease there was
no genotype-phenotype correlation on the basis of the mutation in H1069Q. The qualitative
and quantitative pattern of results do not show any significant differences in the
three groups of genotype. Thus, the time of treatment onset still has most influence
on the extent of clinical manifestation and reversibility of the toxic copper accumulation.
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PD Dr. med. habil. Wieland Hermann
Paracelsus-Klinik Zwickau · Abteilung Neurologie
Werdauer Straße 68
08060 Zwickau
Email: Dr.Wieland.Hermann@pk-mx.de