Wilson Disease

Wilson disease

General Considerations

Wilson disease is a hereditary condition in which defective cellular copper transport leads to excessive deposition of copper in several organs—most commonly the liver, brain, and cornea.

-It is an autosomal recessive disorder caused by mutations in the ATP7B gene on chromosome 13.  

-It usually presents in childhood or young adult life with mean age of onset is between 12 and 23 years of age

Symptoms & Signs

-Wilson disease tends to present as liver disease in adolescents and neuropsychiatric disease in young adults

Hepatic features: acute or chronic liver failure, jaundice, hepatomegaly, cirrhosis, portal hypertension

Neurologic features: basal ganglia dysfunction, tremor, ataxia, incoordination, spasticity, ataxia, migraines, seizures, dysarthria, dysphagia

Psychiatric features: behavioral, personality changes, depression

Miscellaneous: Sunflower cataracts, KF rings, splenomegaly may cause hemolytic anemia and thrombocytopenia.

Kayser-Fleischer ring: Pathognomonic sign of Wilson’s disease; Brownish or gray-green pigmented granular deposits in Descemet membrane in the cornea

Diagnsois

-Decreased serum copper concentration despite the presence of copper overload

-Elevated hepatic copper concentration

-Low serum ceruloplasmin (the plasma copper-carrying protein) level

-Elevated urinary copper excretion

-Testing for mutations in ATP7B can be done and is recommended for a definitive diagnosis.

-Liver biopsy with quantitative copper assays: gold standard for diagnosis

-MRI Brain:  “face of the giant panda” sign in the midbrain and a “face of the miniature panda” in the pontine tegmentum.

Treatment

-Treatment of choice: Copper chelation with D-penicillamine or trientine hydrochloride

Drug of choice: Oral Penicillamine; always add pyridoxine to penicillamine

-Oral zinc acetate (interferes with intestinal absorption of copper)

-Administration of trientine and zinc should be separated by at least 1 hr because trientine chalates zic and forms ineffective complexes

-Tetrathiomolybdate for neurologic therapy

-Patients with Wilson disease require lifelong therapy.

-Liver transplantation for advanced liver disease

Prognosis

-The prognosis of untreated Wilson disease is poor, but it is good if effective treatment occurs before liver or brain damage

  1. What is the most common presentation of Wilson disease? Chronic liver disease
  2. What is the most common ocular finding of Wilson disease? Kayser–Fleischer rings

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