Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy

Arch Neurol. 2003 Mar;60(3):379-85. doi: 10.1001/archneur.60.3.379.

Abstract

Background: It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting.

Objective: To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate.

Design: Open-label study of 55 untreated patients (22 of them new) presenting with neurologic Wilson disease treated with tetrathiomolybdate varying from 120 to 410 mg/d for 8 weeks and then followed up for 3 years. Neurologic function was assessed with scored neurologic and speech tests.

Setting: A university hospital referral setting.

Patients: All untreated, newly diagnosed patients with neurologic Wilson disease.

Intervention: Treatment with tetrathiomolybdate.

Main outcome measures: Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures.

Results: Only 2 (4%) of 55 patients treated with tetrathiomolybdate showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers are higher than in the original 33 patients and appear to be due primarily to a more rapid dose escalation.

Conclusions: Tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Child
  • Enzyme Inhibitors / administration & dosage*
  • Enzyme Inhibitors / adverse effects
  • Female
  • Follow-Up Studies
  • Hepatolenticular Degeneration / complications
  • Hepatolenticular Degeneration / drug therapy*
  • Humans
  • Male
  • Molybdenum / administration & dosage*
  • Molybdenum / adverse effects
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / etiology
  • Neurologic Examination
  • Treatment Outcome
  • Zinc / administration & dosage*

Substances

  • Enzyme Inhibitors
  • Molybdenum
  • tetrathiomolybdate
  • Zinc