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Wilson disease

MIM.277900 13q14.3-q21.1

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.

Epidemiology

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.

Pathology

- copper accumulation
- lesional pattern

  • fatty change (hepatic steatosis)
  • glycogenated nuclei
  • possible massive hepatic necrosis

- clinical patterns

  • fulminant hepatitis
  • chronic hepatitis

Clinical synopsis

- autosomal recessive disease
- Kayser-Fleischer ring
- atypical or prolonged hepatitis
- hepatic cirrhosis
- hepatic coma
- hepatomegaly
- liver failure
- high liver copper
- esophageal varices
- renal tubular dysfunction
- renal calculi
- osteoporosis
- osteomalacia
- chondrocalcinosis
- osteoarthritis
- joint hypermobility
- tremor
- dysarthria
- dysphagia
- personality changes
- dementia
- poor motor coordination
- dystonia
- drooling
- peripheral nervous system
- mixed demyelinating and axonal polyneuropathy (rare)
- hypoparathyroidism
- hemolytic anemia

LABORATORY ABNORMALITIES

- Low serum ceruloplasmin
- High nonceruloplasmin-bound serum copper
- High urinary copper
- Proteinuria
- Aminoaciduria
- Glycosuria
- Uricaciduria
- Hyperphosphaturia
- Hypercalciuria

Etiology

- Wilson disease is caused by mutation in the ATP7B gene (MIM.606882).

Videos

- Wilson disease by Washnington Deceit

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References

- Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML. Wilson’s disease. Lancet. 2007 Feb 3;369(9559):397-408. PMID: 17276780

Portfolio

  • Copper metabolism in the hepatocyte
  • Micronodular cirrhosis in Wilson disease
  • Micronodular cirrhosis in Wilson disease
  • Micronodular cirrhosis in Wilson disease