Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese

Clin Chim Acta. 2001 Nov;313(1-2):157-69. doi: 10.1016/s0009-8981(01)00669-6.


Background: Hyperphenylalaninemia (HPA) may be caused by either a deficiency in phenylalanine-4-hydroxylase or in tetrahydrobiopterin (BH4), the essential cofactor required for the hydroxylation of aromatic amino acids. The most common forms of BH4 deficiency are 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency (MIM 261640) and dihydropteridine reductase (DHPR) deficiency (MIM 261630), which require a different treatment from classical HPA.

Results: Approximately 86% of BH4-deficient HPA in the Chinese population was found to be caused by PTPS deficiency. Eleven missense (73C-->G, 120T-->G, 155A-->G, 166G-->A, 200C-->T, 209T-->A, 226C-->T, 259C-->T, 286G-->A, 317C-->T, 430G-->C), one splicing (IVS3+1G-->A) and two deletion mutations (116-119delTGTT, 169-171delGTG) were identified in 37 unrelated PTPS-deficient Chinese families. Among these, 155A-->G, 259C-->T and 286G-->A mutation accounted for about 80% of the mutant alleles. The 155A-->G and 286G-->A mutations were found to be the common mutation in southern and northern Chinese, respectively. Only two Chinese DHPR-deficient families were detected among about 300 Chinese hyperphenylalaninemia cases. A single base transition 508G-->A on the DHPR cDNA was identified in two consanguineous DHPR-deficient siblings. A reduced level of DHPR mRNA expression was found in the other DHPR-deficient patient, which suggested that the mutation might lie in the regulatory region of the DHPR gene.

Conclusions: The BH4-deficient HPA was estimated to make up around 30% of the Chinese population in Taiwan suffering from HPA, which is much higher than in Caucasian populations (1.5-2% of HPA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / therapeutic use
  • Biopterin / analogs & derivatives*
  • Biopterin / deficiency*
  • Biopterin / therapeutic use
  • Diagnosis, Differential
  • Dihydropteridine Reductase / genetics
  • Female
  • Genetic Carrier Screening
  • Humans
  • Incidence
  • Levodopa / therapeutic use
  • Mass Screening
  • Mutation
  • Phenylketonurias / diagnosis
  • Phenylketonurias / drug therapy
  • Phenylketonurias / epidemiology
  • Phenylketonurias / genetics*
  • Phosphorus-Oxygen Lyases / genetics
  • Pregnancy
  • Prenatal Diagnosis
  • Taiwan / epidemiology
  • Treatment Outcome


  • Biopterin
  • Levodopa
  • 5-Hydroxytryptophan
  • Dihydropteridine Reductase
  • Phosphorus-Oxygen Lyases
  • 6-pyruvoyltetrahydropterin synthase
  • sapropterin

Associated data

  • OMIM/261630
  • OMIM/261640