Friday 30 May 2003
Definition: Progressive hepatolenticular degeneration, or Wilson’s disease, is an autosomal recessive disorder of copper metabolism due to a mutation in the gene ATP7B.
The worldwide prevalence is about 1 in 30,000, which may vary by population. Higher prevalence rates were reported using more sensitive screening techniques and pilot population screening. Incidence in United States of 1 in 55,000. Incidence worldwide of 1 in 30,000 to 50,000
Typical presentations include neuropsychiatric and hepatic dysfunction, whereas atypical presentations are protean.
Diagnosis relies on a high clinical suspicion, typical neurological symptoms, presence of Kayser-Fleischer rings, and reduced serum ceruloplasmin concentration.
The conventional value of < 0.20 g/l is not a universal diagnostic value. Age of the subjects and analytical variations should be considered when interpreting these levels.
Patients with inconclusive findings require further investigations such as 24 h urinary free-copper excretion, penicillamine challenge test, liver copper measurement, and detection of gene mutations.
Direct molecular diagnosis remains the most decisive tool. Other tests such as non-ceruloplasmin-bound copper are unreliable. Potential pitfalls and limitations of these diagnostic markers are critically reviewed in this paper.
The mainstays of therapy are trientine, penicillamine, and/or zinc. Liver transplantation is lifesaving for those with advanced disease.
Ceruloplasmin oxidase activity and serum free-copper concentration should be monitored in patients on long-term de-coppering therapy to prevent iatrogenic copper deficiency.
- fatty change (hepatic steatosis)
- glycogenated nuclei
- possible massive hepatic necrosis
- fulminant hepatitis
- chronic hepatitis
autosomal recessive disease
atypical or prolonged hepatitis
high liver copper
renal tubular dysfunction
poor motor coordination
peripheral nervous system
mixed demyelinating and axonal polyneuropathy (rare)
Low serum ceruloplasmin
High nonceruloplasmin-bound serum copper
High urinary copper
Wilson disease is caused by mutation in the ATP7B gene (MIM.606882).
Wilson disease by Washnington Deceit
Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson’s disease. Lancet. 2007 Feb 3;369(9559):397-408. PMID: #17276780#