RESUMO
INTRODUCTION: Phenylketonuria (PKU), an autosomal recessive metabolic disorder caused by phenylalanine hydroxylase (PAH) deficiency, leads to hyperphenylalaninemia and neurological damage if untreated. This is the first study in the Philippines to identify the disease-causing mutations in the PAH gene of clinically diagnosed Filipino PKU patients. METHODS: The study included four unrelated PKU patients detected by the Philippine Newborn Screening Program from 1996 to 2008. Plasma amino acid analyses for all patients showed increased phenylalanine and low to normal tyrosine levels consistent with the diagnosis of PKU. Mutations in the PAH gene were identified by genomic DNA extraction from dried blood spots of the patients, PAH exon amplification by polymerase chain reaction and subsequent bi-directional DNA sequence analysis. RESULTS: All patients presented with significantly elevated phenylalanine levels on bacterial inhibition assay and thin layer chromatography. Urinary pterins confirmed the diagnosis of Tetrahydrobiopterin deficiency in two patients while the other 2 patients had the Classical PKU phenotype. Four previously identified mutations in the PAH gene (p.I65T, p.R413P, p.EX6-96A>G, p.R243Q) were identified in those with Classical PKU. CONCLUSION: The present results confirm the heterogeneity of mutations at the PAH locus in Filipinos. Neonatal screening and the use of molecular diagnosis significantly aid in the medical management and genetic counseling of patients and their families.