Successful treatment of molybdenum cofactor deficiency type A with cPMP

Pediatrics. 2010 May;125(5):e1249-54. doi: 10.1542/peds.2009-2192. Epub 2010 Apr 12.


Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder characterized by severe and rapidly progressive neurologic damage caused by the functional loss of sulfite oxidase, 1 of 4 molybdenum-dependent enzymes. To date, no effective therapy is available for MoCD, and death in early infancy has been the usual outcome. We report here the case of a patient who was diagnosed with MoCD at the age of 6 days. Substitution therapy with purified cyclic pyranopterin monophosphate (cPMP) was started on day 36 by daily intravenous administration of 80 to 160 microg of cPMP/kg of body weight. Within 1 to 2 weeks, all urinary markers of sulfite oxidase (sulfite, S-sulfocysteine, thiosulfate) and xanthine oxidase deficiency (xanthine, uric acid) returned to almost normal readings and stayed constant (>450 days of treatment). Clinically, the infant became more alert, convulsions and twitching disappeared within the first 2 weeks, and an electroencephalogram showed the return of rhythmic elements and markedly reduced epileptiform discharges. Substitution of cPMP represents the first causative therapy available for patients with MoCD. We demonstrate efficient uptake of cPMP and restoration of molybdenum cofactor-dependent enzyme activities. Further neurodegeneration by toxic metabolites was stopped in the reported patient. We also demonstrated the feasibility to detect MoCD in newborn-screening cards to enable early diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases, Metabolic, Inborn / diagnosis
  • Brain Diseases, Metabolic, Inborn / drug therapy*
  • Coenzymes / deficiency*
  • Diagnosis, Differential
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant, Newborn
  • Infusions, Intravenous
  • Metalloproteins / deficiency*
  • Molybdenum Cofactors
  • Organophosphorus Compounds / therapeutic use
  • Pteridines
  • Pterins / administration & dosage*
  • Pterins / therapeutic use
  • Purine-Pyrimidine Metabolism, Inborn Errors / diagnosis
  • Purine-Pyrimidine Metabolism, Inborn Errors / drug therapy*
  • Sulfite Oxidase / deficiency*


  • Coenzymes
  • Metalloproteins
  • Molybdenum Cofactors
  • Organophosphorus Compounds
  • Pteridines
  • Pterins
  • nulibry
  • pyranopterin
  • molybdenum cofactor
  • Sulfite Oxidase