Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Wilson's Disease (WND) [E83.0]

OMIM numbers: 277900, 606882 (ATP7B)

Dr. rer. nat. Christoph Marschall

Scientific Background

Wilson’s disease is an autosomal recessive disease of the copper metabolism with a prevalence of 1:7,000-30,000. The disease first manifests already within the first days or weeks of life (dyspnea, apnea as well as cyanosis). In 2/3 of all cases, the disease leads to death within the first year of life. Patients who are not affected by the life-threatening, acute phase display signs and symptoms at the age of 20 years on average.

The disease is caused by mutations in the ATP7B gene, which cause the copper binding site of an ATPase in the liver and kidney to be impaired. Low levels of ceruloplasmin cause an increase in free serum copper, despite increased renal excretion of Cu2+. Serum copper has a cytotoxic effect in the tissue. A typical clinical feature of this disease is the golden-brown or green Kayser-Fleischer ring. Neuropsychiatric signs and symptoms during adolescence, such as Parkinson’s-like rigor and tremor, occur frequently. Early diagnosis of the disease is significant, as administration of effective therapeutics can improve the prognosis severely. Wilson’s disease should be ruled out in the case of any unclear liver disease occurring prior to 35 years of age. Laboratory testing shows decrease of ceruloplasmin in the serum; copper excretion in the urine is elevated. Approx. 1/3 of all patients with Wilson’s disease display a transversion of cytosine to adenine, which leads to a His1069Gln amino acid substitution. This mutation (allele frequency approx. 0.3% in Caucasians) has been associated with a relatively mild phenotype and prolonged manifestation of signs and symptoms.