The treatment and clinical follow-up outcome in Iranian patients with tetrahydrobiopterin deficiency.

OBJECTIVES: This study aimed to evaluate the biochemical factors, genetic mutations, outcome of treatment, and clinical follow-up data of Iranian patients with tetrahydrobiopterin (BH4) deficiency from April/2016 to March/2020. METHODS: Forty-seven BH4 deficiency patients were included in the study and underwent biochemical and genetic analyses. The clinical outcomes of the patients were evaluated after long-term treatment. RESULTS: Out of the 47 (25 females and 22 males) BH4 deficiency patients enrolled in the study, 23 were Dihydropteridine reductase (DHPR) deficient patients, 23 were 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficient patients, and one was GTP-Cyclohydrolase 1 deficiency (GTPCH-1) patient. No clinical symptoms were observed in 10 of the DHPR deficient patients (before and after the treatment). Also, most patients diagnosed at an early age had a proper response to the treatment. However, drug therapy did not improve clinical symptoms in three of the patients diagnosed at the age of over 10 years. Also, 16 PTPS deficiency patients who were detected within 6 months and received treatment no clinical symptoms were presented. One of the patients was detected with GTPCH deficiency. Despite being treated with BH4, this patient suffered from a seizure, movement disorder, mental retardation, speech difficulty, and hypotonia. CONCLUSIONS: The study results showed that neonatal screening should be carried out in all patients with hyperphenylalaninemia because early diagnosis and treatment can reduce symptoms and prevent neurological impairments. Although the BH4 deficiency outcomes are highly variable, early diagnosis and treatment in the first months of life are crucial for good outcomes.

Clinical, Biochemical and Genetic Analysis of Biotinidase Deficiency in Iranian Population.

BACKGROUND: Biotinidase deficiency (BTD) is an autosomal recessive disorder of biotin metabolism. Biotin is a coenzyme that enhances the action of the four enzymes that play an important role in carbohydrates, amino acid, and fatty acid metabolism. Defects in these pathways cause severe metabolic disorder in the body. In general, biotinidase deficiency can be classified into two levels: partial and profound. The incidence of BTD is 1:40,000 to 1:60,000 births in the world, even though no convincing statistical data on the prevalence of this disorder exist in Iran. In this study, we aimed to set up a test for determining biotinidase activity among the Iranian population and report BTD mutations. PATIENTS AND METHODS: The quantitative method for the determination of biotinidase activity was set up in the National Biochemistry Reference Laboratory (NBRL) of Pasteur Institute of Iran in Tehran. To detect mutations in BTD, polymerase chain reaction (PCR) was performed followed by DNA sequencing. RESULTS: The biotinidase activity range values were 3.81 - 8.25 nmol/min/mL. We identified 8 BTD patients out of 47 cases with neurologic signs. We detected two mutations, c.98-104del7ins3 and p.Arg79Cys, in 5 patients with profound BTD, and one p.Asp444His mutation in 3 patients with partial BTD. CONCLUSION: Infants suffering from BTD seem healthy during their first months of life. At present, the screening program for metabolic disorders such as BTD is in progress. The patients that are BTD deficient benefit from the availability of the tests, and consequently receive the Biotin supplements before being clinically affected.