Autosomal recessive. Gene (chromosome 13) encodes copper transporting protein. Numerous mutations with variable symptom onset, severity.

Copper abnormalities lead to accumulation of copper in liver (cirrhosis), brain (especially basal ganglia), kidney, cornea (Kayser-Fleischer ring).

Progressive disease, sometimes with temporary clinical arrest or improvement. Symptom onset usually between ages 11 and 25 years.

Ascites, jaundice, esophageal bleeding, other signs of liver damage at any stage.

Neurologic manifestations vary: no characteristic clinical picture. Most common early signs: tremor (often localized to arms; “wing-beating” type), rigidity, psychiatric syndromes. Other findings: dystonia, spasticity of laryngeal or pharyngeal muscles, drooping lower jaw, excess salivation, convulsions, characteristic fixed open-mouth smile.

Tendon reflexes increased; plantar responses almost always flexor. Seizures, usually after starting treatment.

Kayser-Fleischer rings in 75% of patients with hepatic symptoms and 100% those with cerebral symptoms, with or without hepatic symptoms. Never seen before age 7 years.