wilson's disease

1. Wilson’s disease
Abdul Waris Khan
Dept: Internal medicine

2. SOEPEL

4. Definition
• Wilson’s disease is a very rare inborn error of
copper metabolism that results in copper
deposition in various organs, including the
liver, the basal ganglia of the brain and the
cornea. It is potentially treatable.

5. Aetiology
• It is an autosomal recessive disorder with a
molecular defect within a copper-transporting
ATPase encoded by a gene (ATP7B) located on
chromosome 13. The most frequent mutation
being “His1069 Gly (H1069Q)” is seen in
Caucasian patients and is rare in India and
Asia.

6. • Dietary copper is normally absorbed from the
stomach and upper small intestine. It is
transported to the liver loosely bound to
albumin. Here it is incorporated into
apocaeruloplasmin forming caeruloplasmin, a
glycoprotein synthesized in the liver, and
secreted into the blood. The remaining copper
is normally excreted in the bile and excreted in
faeces.

7. Clinical features
• Children usually present with hepatic problems.
• Young adults have more neurological problems,
such as tremor, dysarthria, involuntary
movements and eventually dementia.
• The liver disease varies from episodes of acute
hepatitis, especially in children, which can go on
to fulminant hepatic failure, to chronic hepatitis
or cirrhosis.

9. • A specific sign is the Kayser–
Fleischer ring, which is due to
copper deposition in
Descemet’s membrane in the
cornea. It appears as a greenish
brown pigment at the
corneoscleral junction and
frequently requires slit-lamp
examination for identification.
• It may be absent in young
children.

10. Investigation
• Serum copper and caeruloplasmin are usually reduced but can be
normal.
• Urinary copper is usually increased 100–1000 μg in 24 hours (1.6–
16 μmol); normal levels < 40 μg (0.6 μmol).
• Liver biopsy. The diagnosis depends on measurement of the
amount of copper in the liver (> 250 μg/g dry weight), although
high levels of copper are also found in the liver in chronic
cholestasis.
• Haemolysis and anaemia may be present.
• Genetic analysis is limited but selected exons are screened
according to population group.

11. Treatment
• Lifetime treatment with penicillamine, 1–1.5 g
daily.
• Urine copper levels should be monitored and
the drug dose adjusted downwards after 2–3
years.
• Serious side-effects of the drug occur in 10%
and include skin rashes, leucopenia, skin
changes and renal damage.

12. • Trientine (1.2–1.8 g/day) and zinc acetate (150
mg/day) have been used as maintenance
therapy and for asymptomatic cases.
• All siblings and children of patients should be
screened (ATP7B mutation analysis is useful)
and treatment given even in the
asymptomatic if there is evidence of copper
accumulation.

13. Prognosis
• Early diagnosis and effective treatment have
improved the outlook.
• Neurological damage is, however, permanent.
• Ful-minant hepatic failure or decompensated
cirrhosis should be treated by liver
transplantation.

14. Referenes
• Kumar and Clark clinical medicine 7th edition