Retrospective evaluation of BH4 loading test response and molecular analysis correlation in patients with phenylalanine metabolism disorders

Retrospective evaluation of BH4 Loading Test Response and Molecular Analysis Correlation in Patients with Phenylalanine Metabolism Disorders Hyperphenylalaninemia (HPA) is an autosomal recessive inherited metabolic condition characterized by either deficiency of phenylalanine hydroxylase (PAH), an enzyme responsible for the conversion of an essential amino acid, phenylalanine, to tyrosine in the liver, or deficiency of its cofactor, tetrahydrobiopterin. In this study, demographic features, clinical fenotypes, genotypes, treatments, blood phenylalanine levels at the time of diagnosis, average blood phenylalanine levels during follow-up sessions, BH4 responsiveness, mental status and continuity of the care in patients with phenylalanine metabolism disorders were retrospectively evaluated. The purpose of this study was to investigate the possibility of BH4 loading test response prediction by different genetic mutations. We collected detailed data of 329 patients with phenylalanine metabolism disorder, referred to Pediatric Metabolism Clinics at Bursa Uludag University, Faculty of Medicine between 1 June 2011 and 1 November 2018. Mutation analysis was performed for 242 of them. BH4 loading test results of 82 (%25) of 329 patients revealed that 51 (%62.2) of the tests were positive. Of the patients with a positive BH4 loading test, 41 patients (%80.4) showed mild HPA phenotype, 7 of them (%13.7) showed mild PKU phenotype and 3 of them (% 5.9) showed classic PKU phenotype. The most common mutation was IVS10-11G>A for all patients included in the study. The most common mutations for the patients who underwent BH4 treatment were c.1169A>G, c.782G>A, IVS10-11G>A c.721C>T, c.898G>T, c.631C>A respectively. To conclude; in this study, it was shown that it is possible to estimate BH4 loading test response by genetic mutation analysis. The patients with higher enzyme levels which were grouped into mild HPA or mild PKU had a higher tendency of positive test results. We should consider BH4 loading test or BH4 treatment for those patients whose blood phenylalanine levels tend to increase during follow-ups. Keywords: Hyperphenylalaninemia, child, BH4, genotype