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.