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

Abstract

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.

Detection of IVS4+1G>A mutation in phenylalanine hydroxylase gene in North of Iran using PCR-sequencing

“…This level is less than 2 mg/dL in healthy children, 2-10 in HPA patients, 10-15 in mild PKU, 15-20 in moderate PKU, and more than 20 mg/dL in classic PKU (3). In addition, 98% of all cases of HPA are related to mutations in the PAH gene (4). Mutation in the genes that are involved in the synthesis and metabolism of the cofactor tetrahydrobiopterin such as PTS, GCH1, QDPR, and PCBD1 accounts for the other 2% of HPA cases (3).…”