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


METHODS
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.


METHODS
A university hospital referral setting.


METHODS
All untreated, newly diagnosed patients with neurologic Wilson disease.


METHODS
Treatment with tetrathiomolybdate.


METHODS
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.
Brewer
George J
GJ
Department of Human Genetics, University of Michigan Medical School, 4909 Buhl, Ann Arbor, MI 48109-0618, USA. brewergj@umich.edu
Hedera
Peter
P
Kluin
Karen J
KJ
Carlson
Martha
M
Askari
Fred
F
Dick
Robert B
RB
Sitterly
Julia
J
Fink
John K
JK
D000328:Adult; D002648:Child; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008982:Molybdenum / Q000008:administration & dosage* / Q000009:adverse effects; D009422:Nervous System Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination; D016896:Treatment Outcome; D015032:Zinc / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D008982:Molybdenum; C020809:tetrathiomolybdate; D015032:Zinc