Define Wilson Disease. Describe its clinical features, investigations, management and diagnosis.

Definition

• Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene.
• Impaired biliary copper excretion leads to copper accumulation in the liver, brain, cornea and other tissues.

Clinical Features

• Hepatic (younger children) — ranges from asymptomatic transaminitis to acute hepatitis, chronic liver disease, cirrhosis or acute liver failure.
• Neurological (older children/adolescents) — dystonia, tremor, dysarthria, drooling, deteriorating handwriting and school performance.
• Psychiatric — behavioural change, depression.
• Kayser-Fleischer rings — golden-brown copper deposits at the corneal margin (seen on slit-lamp).

Investigations

• Low serum ceruloplasmin; raised 24-hour urinary copper (further rising after a penicillamine challenge).
• Kayser-Fleischer rings on slit-lamp examination.
• Raised hepatic copper on liver biopsy; genetic testing for ATP7B.

Management

• Copper chelation — D-penicillamine or trientine (promote urinary copper excretion).
• Zinc — blocks intestinal copper absorption (maintenance/pre-symptomatic).
• Low-copper diet — avoid liver, shellfish, nuts, chocolate, mushrooms.
• Liver transplantation for acute liver failure or decompensated cirrhosis; screen siblings.

WHY Early Diagnosis Matters

• Wilson disease is a treatable cause of chronic liver disease and neurological deterioration — untreated it is progressive and fatal, but with chelation it is largely controllable.
• Hence every child over ~3 years with unexplained liver disease, or a young person with a movement disorder, should be screened.

A Diagnostic Caveat

Ceruloplasmin can be falsely normal (an acute-phase reactant) or low in other conditions, so the diagnosis rests on a combination of tests — ceruloplasmin, urinary copper, KF rings, and (if needed) hepatic copper/genetics.