Medication Summary
The mainstay of therapy for Wilson disease is the use of chelating agents and medications that block copper absorption from the gastrointestinal (GI) tract.
Zinc and penicillamine are lifelong medications for patients with Wilson disease. Dosages vary with the severity of the disorder. Another chelating agent is trientine, which may be more easily tolerated than penicillamine. [21] Patients who do not respond to zinc therapy and who have increased activities of liver enzymes should be identified so that chelating agents may be added to the therapeutic regimen. [22, 23]
Other medications used to treat Wilson disease include anticholinergics, baclofen, gamma-aminobutyric acid (GABA) antagonists, and levodopa, to treat parkinsonism and dystonia symptoms; antiepileptics to treat seizures; and neuroleptics to treat psychiatric symptoms. In addition, protein restriction, lactulose, or both are used to treat hepatic encephalopathy.
Chelators
Class Summary
Chelating agents bind excess copper. Ammonium tetrathiomolybdate is an investigational chelating drug used at the University of Michigan as an initial treatment for patients who present with neurologic or psychiatric manifestations. This drug works as a chelating agent and as an inhibitor of copper absorption from the GI tract. [24]
Penicillamine (Cuprimine, Depen)
Penicillamine forms soluble complexes with metals excreted in urine. It was the drug of choice before newer regimens were available. Because of extensive toxicities, alternative agents are used. It must be administered with pyridoxine 25 mg by mouth daily.
Trientine (Syprine)
Trientine is an effective oral chelator used to induce cupruresis. It is useful for patients who cannot tolerate penicillamine. It is indicated in Wilson disease if the initial presentation is hepatic. It should be administered with zinc.
Dimercaprol (BAL in Oil)
Dimercaprol is for refractory cases of Wilson disease that are not responding to first- or second-line chelation treatment.
Nutrients
Class Summary
Nutrients are essential to normal growth and development, and they play a role in many metabolic processes.
Zinc (Galzin)
Zinc is a cofactor for more than 70 types of enzymes. It is approved for patients initially treated with a chelating agent. It should be used for maintenance after initial chelation therapy. Zinc acetate is the drug of choice in presymptomatic, pregnant, pediatric populations, and in some instance for maintenance in compliant patients who have undergone copper chelation therapy. It is a second-line therapy in patients with neurologic manifestations who do not tolerate chelation as a consequence of deterioration on this therapy.
Pyridoxine (Aminoxin, Pyri-500)
Pyridoxine is involved in synthesis of GABA within the CNS.
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Computed tomography (CT) scan in a 15-year-old boy who presented with central nervous system findings consistent with Wilson disease. The CT scan reveals hypodense regions in the basal ganglia (caudate nucleus, putamen, globus pallidus). The differential diagnosis based on this image alone included leukodystrophy, vasculitis, and, less likely, infection. Ventricular enlargement and posterior fossa atrophy may also be seen on brain CT scans in a patient with Wilson disease. The extent of involvement as depicted on CT scans does not provide prognostic information.
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Approach to the diagnosis of Wilson disease (WD) in a patient with unexplained liver disease. KF = Kayser-Fleischer ring; CPN = ceruloplasmin. From the American Association for the Study of Liver Diseases Practice Guidelines.
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In this particular case, there is abundant Mallory hyaline. Another notable finding is the moderate to marked chronic inflammation which involved most portal tracts and periportal/perinodular areas.
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Prismaflex eXeed II adds citrate anticoagulation with integrated calcium management. Image courtesy of Gambro.
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Molecular adsorbents recirculating system (MARS) circuit.
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Biopsy specimen showing hepatocellular injury in an explant specimen from a patient transplanted for Wilson Disease.
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Biopsy specimen showing a more detailed image of the cellular injury in acute Wilson disease.
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Wilson disease biopsy specimen with rhodanine stain.
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Wilson disease biopsy specimen with rhodanine stain (stain specific for copper deposition).
Tables
Score |
0 |
1 |
2 |
3 |
4 |
Serum bilirubin (reference range, 3-20 mmol/L) |
< 100 |
100-150 |
151-200 |
201-300 |
>300 |
Serum aspartate transaminase (reference range, 7-40 IU/L) |
< 100 |
100-150 |
151-200 |
201-300 |
>300 |
Prothrombin time prolongation (seconds) |
< 4 |
4-8 |
9-12 |
13-20 |
>30 |
