Successful treatment of molybdenum cofactor deficiency type a with cyclic pyranopterin monophospate (CPMP).

Molybdenum cofactor (Moco) deficiency (MoCD) is a rare metabolic disorder characterized by severe and rapidly progressive neurological damage caused by the functional loss of sulfite oxidase. To date, no effective therapy has been available for MoCD and death in early infancy has been the usual outcome. A Moco-deficient patient was been diagnosed at the age of 6 days, which was found to be MOCS1-deficient causing the absence of cyclic pyranopterin monophospate (cPMP), a precursor of Moco. A substitution therapy with purified cPMP was started on day 36 by daily administration of 80-160 mug cPMP / kg body weight by intravenous infusion. All urinary markers of sulfite oxidase (sulfite, S-sulfocystein, thiosulfate) and xanthine oxidase deficiency (xanthine, uric acid) returned to almost normal readings within 1-2 weeks after treatment and stayed constant (>500 days of treatment). Clinically, the patient became more alert few days after treatment started, convulsions and twitching disappeared within the first two weeks as documented by an EEG showing the return of rhythmic elements and markedly reduced epileptiform discharges. In addition, two other recently treated cases will be presented. Substitution of cPMP represents the first causative therapy available for MoCD patients. We also demonstrated the feasibility to detect MoCD in newborn screening cards to enable early diagnosis.