Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect

Clin Genet. 2015 Jul;88(1):62-7. doi: 10.1111/cge.12444. Epub 2014 Jul 26.


The mutational spectrum of the phenylalanine hydroxylase gene (PAH) in Mexico is unknown, although it has been suggested that PKU variants could have a differential geographical distribution. Genotype-phenotype correlations and genotype-based predictions of responsiveness to tetrahydrobiopterin (BH4 ) have never been performed. We sequenced the PAH gene and determined the geographic origin of each allele, mini-haplotype associated, genotype-phenotype correlations and genotype-based prediction of BH4 responsiveness in 48 Mexican patients. The mutational spectrum included 34 variants with c.60+5G>T being the most frequent (20.8%) and linked to haplotype 4.3 possibly because of a founder effect and/or genetic drift. Two new variants were found c.1A>T and c.969+6T>C. The genotype-phenotype correlation was concordant in 70.8%. The genotype-based prediction to BH4 -responsiveness was 41.7%, this information could be useful for the rational selection of candidates for BH4 testing and therapy.

Keywords: PKU; hyperphenylalaninemia; phenylketonuria; tetrahydrobiopterin.

MeSH terms

  • Biopterins / analogs & derivatives*
  • Biopterins / therapeutic use
  • Child, Preschool
  • DNA Mutational Analysis
  • Founder Effect*
  • Genetic Association Studies*
  • Haplotypes
  • Humans
  • Mexico
  • Mutation*
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / drug therapy
  • Phenylketonurias / genetics*
  • Treatment Outcome


  • Biopterins
  • Phenylalanine Hydroxylase
  • sapropterin