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