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The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness

  • Gladys Ho
  • Ian Alexander
  • Kaustuv Bhattacharya
  • Barbara Dennison
  • Carolyn Ellaway
  • Sue Thompson
  • Bridget Wilcken
  • John Christodoulou
Research Report
Part of the JIMD Reports book series (JIMD, volume 14)

Abstract

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism predominantly caused by mutations in the phenylalanine hydroxylase (PAH) gene. Mutation screening was carried out in a large cohort of PKU patients from New South Wales, Australia. Pathogenic mutations were identified in 99% of the alleles screened, with the two most common mutations (p.R408W and IVS12+1G>A) accounting for 30.7% of alleles. Most individuals were compound heterozygotes for previously reported mutations, but four novel mutations (c.163+1G>T, c.164-2A>G, c.461A>T [p.Y154F], and c.510-1G>A) and a novel polymorphism (c.60+62C>T) were also identified. A number of patients have been previously tested for their response to dietary supplementation of tetrahydrobiopterin (BH4), the cofactor of PAH. Correlation between genotype and the responses revealed that although genotype is a major determinant of BH4 responsiveness, patients with the same genotype may also show disparate responses to this treatment. A clinical and biochemical evaluation should be undertaken to determine the effectiveness of PKU treatment by supplementation of BH4.

Keywords

Pathogenic Mutation Compound Heterozygote Phenylalanine Hydroxylase Autosomal Recessive Inborn Error Translation Initiation Start 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

This research was supported by donations from the NSW PKU Association and from the Rotary Club of Pennant Hills.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Gladys Ho
    • 1
    • 2
  • Ian Alexander
    • 2
    • 3
    • 4
  • Kaustuv Bhattacharya
    • 2
    • 3
    • 4
  • Barbara Dennison
    • 4
    • 5
  • Carolyn Ellaway
    • 2
    • 3
    • 4
  • Sue Thompson
    • 4
    • 5
  • Bridget Wilcken
    • 2
    • 3
    • 4
  • John Christodoulou
    • 1
    • 2
    • 3
    • 4
  1. 1.Genetic Metabolic Disorders Research UnitChildren’s Hospital at WestmeadWestmeadAustralia
  2. 2.Discipline of Paediatrics and Child HealthUniversity of SydneySydneyAustralia
  3. 3.Discipline of Genetic MedicineUniversity of SydneySydneyAustralia
  4. 4.Genetic Metabolic Disorders Service, Western Sydney Genetics ProgramChildren’s Hospital at WestmeadWestmeadAustralia
  5. 5.Dept of Nutrition and DieteticsChildren’s Hospital at WestmeadWestmeadAustralia

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