Dihydropteridine reductase (DHPR) deficiency is a genetic disorder of tetrahydrobiopterin (BH4) regeneration and may present with hyperphenylalaninemia, microcephaly, hypotonia, mental retardation, and convulsions. BH4 is an essential cofactor for the hydroxylation of aromatic amino acids and a deficiency of BH4 results in decreased synthesis of dopamine and serotonin. We present a 27-month-old female patient with DHPR deficiency who was treated with l-dopa/carbidopa (2 mg/kg, four times per day), 5-hydroxytryptophan (2 mg/kg, four times per day), folinic acid (10 mg/day), and BH4 supplementation (20 mg/kg, twice a day). Although remarkable clinical improvement with normal plasma phenylalanine (Phe) levels and increased phenylalanine tolerance was noted 1 month after the treatment, CSF neurotransmitter metabolites did not improve. BH4 supplementation was increased to 40 mg/kg/day and the CSF study was repeated 1 month later. There was no significant change of CSF neurotransmitters, BH4 or BH2 levels but plasma Phe level was within normal range. Surprisingly, she had developmental improvement noted at 1-month and 3-month visits following an augmented neurotransmitter and BH4 treatment. She was able to pull herself to the standing position and sit down on her own. She was also noted to be more alert and responsive following treatment. Her expressive language did not improve, although her receptive language was markedly improved. The above treatment improved patient’s clinical findings, normalized blood Phe levels, and increased Phe tolerance in the diet, but neither 20 nor 40 mg/kg/day BH4 supplementation corrected neurotransmitter or BH4 levels or increased BH2 level in CSF. Further studies are needed to find the optimal management plan for patients with DHPR deficiency.
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Cerebral spinal fluid
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al Aqeel A, Ozand PT, Gascon GG, Hughes H, Reynolds CT, Subramanyam SB (1992) Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin. J Child Neurol 7:S26–30PubMedCrossRefGoogle Scholar
Blau N, Barnes I, Dhondt JL (1996) International database of tetrahydrobiopterin deficiencies. J Inherit Metab Dis 19:8–14PubMedCrossRefGoogle Scholar
Brand MP, Hyland K, Engle T, Smith I, Heales SJR (1996) Neurochemical effects following peripheral administration of tetrahydropterin derivatives to the hph-1 mouse. J Neurochem 66:1150–1156PubMedCrossRefGoogle Scholar
Dahl HH, Hutchison W, McAdam W, Wake S, Morgan FJ, Cotton RG (1987) Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency. Nucleic Acids Res 15:1921–1932PubMedCrossRefGoogle Scholar
Dianzani I, de Sanctis L, Smooker PM et al (1998) Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. Hum Mutat 12:267–273PubMedCrossRefGoogle Scholar
Howells DW, Forrest SM, Dahl HH, Cotton RG (1990) Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency. Am J Hum Genet 47:279–285PubMedGoogle Scholar
Irons M, Levy HL, O'Flynn ME et al (1987) Folinic acid therapy in treatment of dihydropteridine reductase deficiency. J Pediatr 110:61–67PubMedCrossRefGoogle Scholar
Kaufman S, Kapatos G, McInnes RR, Schulman JD, Rizzo WB (1982) Use of tetrahydropterins in the treatment of hyperphenylalaninemia due to defective synthesis of tetrahydrobiopterin: evidence that peripherally administered tetrahydropterins enter the brain. Pediatrics 70:376–380PubMedGoogle Scholar
Ponzone A, Guardamagna O, Dianzani I et al (1993) Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment. Pediatr Res 33:125–128PubMedCrossRefGoogle Scholar
Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L (2004) Dihydropteridine reductase deficiency in man: from biology to treatment. Med Res Rev 24:127–150PubMedCrossRefGoogle Scholar
Smith I, Hyland K, Kendall B (1985) Clinical role of pteridine therapy in tetrahydrobiopterin deficiency. J Inherit Metab Dis 8(Suppl 1):39–45PubMedCrossRefGoogle Scholar