Wilson's disease

Background

• Autosomal recessive
• Impairment of biliary cellular copper excretion with accumulation in organs (mostly liver, brain, cornea)
• Liver becomes cirrhotic with ~5% developing liver failure

Clinical Features

Under slit-lamp test, Kayser-Fleischer ring is evident around the border of cornea (arrow).

Another example of Kayser–Fleischer ring (brown ring on the edge of the iris).

Copper deposition on corneal Descemet's membrane on slit lamp exam.

• Hepatic
  • Kayser-Fleischer rings (highly specific)
  • Asymptomatic (steatosis, chronic hepatitis, compensated cirrhosis)
  • Abdominal pain (acute liver failure/hepatitis)
  • Jaundice, hepatomegaly, splenomegaly, ascites
  • Upper GI bleeding; sequela of cirrhosis with varices
• Neurologic symptoms
  • Dysarthria
  • Gait abnormalities
  • Dystonia
  • Tremor
  • Parkinsonism
• Psychiatric symptoms
  • Depression, personality changes, impulsiveness, psychosis

Differential Diagnosis

Hepatic dysfunction

Infectious

• Hepatitis
• Malaria
• HIV (present in 50% of AIDS patients)
• EBV
• Babesiosis, leptospirosis
• Typhoid
• Hepatic abscess, amebiasis

Neoplastic

• Metastases
• Hepatocellular carcinoma
• Multiple myeloma
• Leukemia
• Lymphoma
• Myeloproliferative disorders

Metabolic

• Hemochromatosis
• Wilson's disease
• Non-alcoholic steatohepatitis
• Inborn errors of metabolism

Biliary

• Biliary cirrhosis

Drugs

• Alcoholic cirrhosis
• Alcoholic hepatitis
• Hepatotoxic drugs

Miscellaneous

• Veno-occlusive disease
• CHF (right heart failure)

Neuro/psychiatric symptoms

• Essential tremor
• Parkinson's disease
• Generalized dystonia
• Primary psychiatric disorder (e.g. depression, bipolar disorder, schizophrenia
• Dementia
• Drug abuse

Evaluation

• LFTs to assess ALT/AST
• CBC to assess for anemia (followed by testing for Coombs-negative hemolytic anemia)
• Ocular slit-lamp to assess for Kayser-Flesicher rings
• Outpatient ceruloplasmin concentration, serums copper concentration, 24-hour urinary copper excretion +/- genetic testing can be done to confirm diagnosis
• Hepatology consult should be made for follow up

Management

• Potent chelators: D-penicillamine (first-line), trientine (second-line), oral zinc
• Low-copper diet
• Screening for hepatocellular carcinoma (HCC) recommended but unclear association

References

1. Lorincz MT. Neurologic Wilson's disease. Ann N Y Acad Sci 2010; 1184:173.
2. Gollan JL, Gollan TJ. Wilson disease in 1998: genetic, diagnostic and therapeutic aspects. J Hepatol 1998; 28 Suppl 1:28.
3. Soltanzadeh A, Soltanzadeh P, Nafissi S, et al. Wilson's disease: a great masquerader. Eur Neurol 2007; 57:80.
4. Stremmel W, Meyerrose KW, Niederau C, et al. Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 1991; 115:720.