SCIENTIFIC BACKGROUND

ATP7B

Wilson disease is a rare autosomal recessive disorder of copper metabolism with a prevalence of 1:7,000-1:30,000. Initial manifestations of the disease can be observed in the first days or weeks of life (dyspnea, apnea, and cyanosis). In 2/3 of cases the disease leads to death within the first year of life. Patients not affected by the life-threatening acute phase present with symptoms at an average age of 20 years old.

 

The disease is caused by pathogenic variants in the ATP7B gene, which disrupts the copper-binding region of an ATPase in the liver and kidney. There is an increase in free serum copper with decreased ceruloplasmin despite increased renal Cu2+ excretion, which has a cytotoxic effect in tissues.

 

A typical clinical feature of this disease is the golden-brown-green Kayser-Fleischer corneal ring. Neurological-psychiatric symptoms in adolescence, such as Parkinson-like rigor and tremor, are also common. Because effective therapeutics exist that significantly improve prognosis, early diagnosis of the condition is of particular importance. Wilson disease should be ruled out in any unexplained liver disease that occurs before the age of 35. Laboratory chemistry shows decreased serum ceruloplasmin and increased urinary copper excretion. Approximately 1/3 of patients with Wilson disease have a transversion from cytosine to adenine leading to a His1069Gln amino acid exchange. This variant (allele frequency approximately 0.3% in the Caucasian population) is associated with a relatively mild phenotype and delayed manifestation of symptoms.

 

References
Hermann & Huster 2018, Nervenarzt 89:115; Weiss KH. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® (Updated 2016); Coffey et al. 2013, Brain 136:1476; Moller et al. 2011, Eur J Hum Genet 19:335; Mak et al. 2008, J Hum Genet 53:55

GENES

ATP7B

ASSOCIATED TESTS

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