The proportion of tetrahydrobiopterin deficiency and PAH gene deficiency variants among cases with hyperphenyalaninemia in Western Iran.

BACKGROUND: Defects either in phenylalanine hydroxylase (PheOH) or in the production and recycling of its cofactor (tetrahydrobiopterin [BH4]) are the causes of primary hyperphenylalaninemia (HPA). The aim of our study was to investigate the current status of different variants of HPA Kurdish patients in Kermanshah province, Iran. MATERIALS AND METHODS: From 33 cases enrolled in our study, 32 were identified as HPA patients. Reassessing of pre‑treatment phenylalanine concentrations and the analysis of urinary pterins was done by high‑performance liquid chromatography method. RESULTS: A total of 30 patients showed PAH deficiency and two patients were diagnosed with BH4 deficiency (BH4/ HPA ratio = 6.25%). Both of these two BH4‑deficient patients were assigned to severe variant of dihydropteridine reductase (DHPR) deficiency. More than 75% of patients with PAH deficiency classified as classic phenylketonuria (PKU) according their levels of pre‑treatment phenylalanine concentrations. CONCLUSION: Based on the performed study, we think that the frequency of milder forms of PKU is higher than those was estimated before and/or our findings here. Furthermore, the frequency of DHPR deficiency seems to be relatively high in our province. Since the clinical symptoms of DHPR deficiency are confusingly similar to that of classic PKU and its prognosis are much worse than classical PKU and cannot be solely treated with the PKU regime, our pilot study support that it is crucial to set up screening for BH4 deficiency, along with PAH deficiency, among all HPA patients diagnosed with HPA.

A Case of Dihydropteridine Reductase Deficiency

Tetrahydrobiopterin (BH4) deficiency is caused by mutations in genes encoding enzymes involved in the synthesis and regeneration of BH4. The condition is usually accompanied by hyperphenylalaninemia (HPA) and deficiency of neurotransmitter precursors L-dopa and 5-hydroxytryptophan. BH4 deficiency is much rarer than classical phenylketonuria. Dihydropteridine reductase (DHPR) deficiency, an autosomal recessive genetic disorder, is a cause of malignant hyperphenylalaninemia due to BH4 deficiency. When left untreated, DHPR deficiency leads to neurologic deterioration at the age of 4 or 5 months, including psychomotor retardation, tonicity disorders, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Treatment of DHPR deficiency should be initiated as early as possible with BH4 supplementation and replacement of the neurotransmitter precursors L-dopa and 5-hydroxytryptophan. We report the first case of DHPR deficiency in Korea, a child diagnosed at 9 years of age by genetic testing.