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Fortschr Neurol Psychiatr 2006; 74(10): 558-566
DOI: 10.1055/s-2005-919084
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Klinische und Genotyp-Phänotyp-Korrelation epidemiologischer, bildgebender und neurologischer Befunde bei Patienten mit Morbus Wilson

Correlation of Clinical Aspects as Well as Genotype and Phenotype in Wilson's Disease on the Basis of Epidemiologic, Clinical and Cranial MRI FindingsW.  Hermann1 , P.  Günther1 , J.  P.  Schneider1 , T.  Villmann1 , H.  J.  Kühn1 , S.  Eichelkraut1
  • 1Paracelsusklinik Zwickau (Direktor: Prof. Dr. med. Gerhard Reichel)
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Publication Date:
02 January 2006 (online)

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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