Treatment of Wilson disease with ammonium tetrathiomolybdate. II. Initial therapy in 33 neurologically affected patients and follow-up with zinc therapy
G. J. Brewer, V. Johnson, R. D. Dick, K. J. Kluin, J. K. Fink and J. A. Brunberg
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, USA.
OBJECTIVE: To test the efficacy and toxic effects of ammonium
tetrathiomolybdate in the initial treatment of a relatively large series of
patients with neurologic symptoms and signs caused by Wilson disease. Two
key aspects of efficacy are to preserve the neurologic function present at
the onset of therapy and to maximize the opportunity for long-term
recovery. DESIGN: An open study of 33 patients treated for 8 weeks each,
including further follow-up data on the original 17 patients. Neurologic
function was evaluated by frequent quantitative neurologic and speech
pathology examinations. Several copper-related variables were studied to
evaluate the effect of the drug on copper, and several biochemical and
clinical variables were studied to evaluate potential toxic effects.
Patients were then followed up at yearly intervals, with follow-up periods
of 1 to 8 years reported. SETTING: A university hospital referral setting.
INTERVENTION: Patients were generally treated for 8 weeks with
tetrathiomolybdate, followed by zinc maintenance therapy. MAIN OUTCOME
MEASURES: Neurologic function was evaluated by quantitative neurologic and
motor speech examinations and magnetic resonance imaging scans of the
brain. RESULTS: During the 8 weeks of tetrathiomolybdate administration,
only 1 of the 33 patients showed deterioration in neurologic function.
Copper status and potential further toxic effects were generally well
controlled quickly. Evaluation of data from individual patients revealed
evidence of a toxic side effect in only 1 patient, who exhibited reversible
anemia. During the ensuing period of follow-up of 1 to 6 years, neurologic
recovery in most patients was good to excellent. CONCLUSIONS:
Tetrathiomolybdate appears to be an excellent form of initial treatment in
patients with Wilson disease who present with neurologic symptoms and
signs. In contrast to penicillamine therapy, initial treatment with
tetrathiomolybdate rarely allows further, often irreversible, neurologic
deterioration.