Mutational and phenotypical spectrum of phenylalanine hydroxylase deficiency in Denmark

Clin Genet. 2016 Sep;90(3):247-51. doi: 10.1111/cge.12692. Epub 2015 Dec 12.


We describe the genotypes of the complete cohort, from 1967 to 2014, of phenylketonuria (PKU) patients in Denmark, in total 376 patients. A total of 752 independent alleles were investigated. Mutations were identified on 744 PKU alleles (98.9%). In total, 82 different mutations were present in the cohort. The most frequent mutation c.1315+1G>A (IVS12+1G>A) was found on 25.80% of the 744 alleles. Other very frequent mutations were c.1222C>T (p.R408W) (16.93%) and c.1241A>G (p.Y414C) (11.15%). Among the identified mutations, five mutations; c.532G>A (p.E178K), c.730C>T (p.P244S), c.925G>A (p.A309T), c.1228T>A (p.F410I), and c.1199+4A>G (IVS11+4A>G) have not been reported previously. The metabolic phenotypes of PKU are classified into four categories; 'classical PKU', 'moderate PKU', 'mild PKU' and 'mild hyperphenylalaninemia'. In this study, we assigned the phenotypic outcome of three of the five novel mutations and furthermore six not previously classified mutations to one of the four PKU categories.

Keywords: PAH; PKU; classification; genotype-phenotype.

MeSH terms

  • Alleles
  • Denmark
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Phenylalanine Hydroxylase / genetics*
  • Phenylketonurias / diagnosis
  • Phenylketonurias / genetics*
  • Phenylketonurias / pathology


  • Phenylalanine Hydroxylase