title: 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.
  
  
  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.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, 4909 Buhl, Ann Arbor, MI 48109-0618, USA. brewergj@umich.edu
authors.forename: George J
authors.initials: GJ
authors.lastname: Brewer
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Kluin
authors.forename: Martha
authors.initials: M
authors.lastname: Carlson
authors.forename: Fred
authors.initials: F
authors.lastname: Askari
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dick
authors.forename: Julia
authors.initials: J
authors.lastname: Sitterly
authors.forename: John K
authors.initials: JK
authors.lastname: Fink
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D008982:Molybdenum; C020809:tetrathiomolybdate; D015032:Zinc