Young Girl With Clumsiness, Dystonia, and Speech Difficulty

Sidra Aurangzeb, MBBS; Muhammad Tariq, MRCP, FRCP, FRCPE


June 24, 2015

Once Wilson disease is diagnosed in an index patient, an evaluation of his or her family is mandatory. The likelihood of finding a homozygote among the patient's siblings is 25%, and it is 0.5% among the patient's children. Testing of second-degree relatives is useful only if the gene is found in one of the immediate members of the relative's family.

No single biochemical test is able to identify affected siblings or heterozygote carriers of the Wilson disease gene with sufficient certainty. Today, testing for ATP7B mutations or haplotype analysis can be used as primary screening of first-degree relatives. In haplotype analysis, numerous highly polymorphic microsatellite markers of dinucleotides or trinucleotides that closely flank the gene allow Wilson disease to be traced in a family. For such an analysis, at least one first-degree relative and the index patient are required.[4]

According to the recently updated American Association for the Study of Liver Diseases practice guidelines on Wilson disease, initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients and maintenance therapy in successfully treated symptomatic patients can also be accomplished with these chelating agents or, alternatively, with zinc. Liver transplantation, which corrects the underlying hepatic defect in Wilson disease, is reserved for patients with acute liver failure and those with decompensated liver disease that is resistant to medical therapy.

Treatment with penicillamine is still the criterion standard; the major effect of this compound is chelation and subsequent urinary excretion. Most symptomatic patients, whether hepatic, neurologic, or psychiatric, respond within months of starting treatment. Among patients with neurologic Wilson disease, a significant proportion (10%-50%) may experience an initial worsening of symptoms before they improve.

Trientine is also a copper chelator that acts primarily by enhancing urinary copper excretion. It is approved for the treatment of Wilson disease and is as effective as penicillamine, with far fewer side effects.

Zinc interferes with intestinal absorption of copper and increases fecal excretion of copper. The experience with other drugs is very limited; ammonium tetrathiomolybdate is currently experimental in the United States, but it appears to be useful for the initial treatment of patients with neurologic symptoms. Antioxidants, mainly vitamin E, may also have a role as adjunctive treatment, but no rigorous studies have been conducted.[1,2,3,4]

Patients should avoid foods with a high copper content, such as liver, broccoli, legumes, chocolate, nuts, mushrooms, and shellfish (particularly lobster). Drinking water from atypical sources (eg, well water) should be tested for copper concentration and replaced with purified water if greater than 0.2 parts per million of copper are found. Also, patients should avoid alcohol consumption and potentially hepatotoxic drug therapy.[2,3,4]

The patient in this case was started on penicillamine 500 mg three times daily, along with dietary restriction of copper-containing foods. She was followed in the neurology outpatient clinic and showed considerable improvement 6 months after therapy.


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