Two mutations ofdihydropteridine reductase deficiency

SUMMARY Twopatients withdihydropteridine reductase (DHPR)deficiency, inone casedueto theabsence ofany enzyme protein (DHPR-crossreactive material (CRM)-)andintheother caseduetotheproduction ofa mutanttypedevoid ofcatalytic activity (DHPR-CRM+)were examined. Thislatter formofmalignant phenylketonuria, whoserelative frequency seems tobe higher intheItalian population, possibly hasa worse prognosis. Theearlier onsetandthegreater severity ofclinical symptomsare associated witha more pronounced hydroxylation defect, as shownbyhigher degree ofneonatal hyperphenylalaninaemia, unresponsiveness to an oral tetrahydrobiopterin load, lowerconcentrations ofneurotransmitter metabolites, andreduced tyrosine production after an oralphenylalanine load.