Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese.
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).
Liu
T T
TT
Institute of Genetics, National Yang-Ming University, Taipei, Taiwan, ROC.
Chiang
S H
SH
Wu
S J
SJ
Hsiao
K J
KJ
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004093:Dihydropteridine Reductase / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D015994:Incidence; D007980:Levodopa / Q000627:therapeutic use; D008403:Mass Screening; D009154:Mutation; D010661:Phenylketonurias / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome
D001708:Biopterins; D007980:Levodopa; D006916:5-Hydroxytryptophan; D004093:Dihydropteridine Reductase; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin