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

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.

• Authors: George J Brewer, Peter Hedera, Karen J Kluin, Martha Carlson, Fred Askari, Robert B Dick, Julia Sitterly, John K Fink
• Journal: Archives of neurology (Arch Neurol) Vol. 60 Issue 3 Pg. 379-85 (Mar 2003) ISSN: 0003-9942 [Print] United States
• PMID: 12633149 (Publication Type: Clinical Trial, Journal Article, 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.)

Chemical References

• Enzyme Inhibitors
• Molybdenum
• tetrathiomolybdate
• Zinc

Topics

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