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).

• 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.