Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese

Background: Hyperphenylalaninemia (HPA) may be caused by either a deficienc y in phenylalanine-4-hydroxylase or in tetrahydrobiopterin (BH4), the essen tial cofactor required for the hydroxylation of aromatic amino acids. The m ost common forms of BH4 deficiency are 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency (MIM 261640) and dihydropteridine reductase (DHPR) defic iency (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) an d two deletion mutations (116-119delTGTT, 169-171delGTG) were identified in 37 unrelated PTPS-deficient Chinese families. Among these, 155A --> G, 259 C --> T and 286G --> A mutation accounted for about 80% of the mutant allel es. The 155A --> G and 286G --> A mutations were found to be the common mut ation in southern and northern Chinese, respectively. Only two Chinese DHPR -deficient families were detected among about 300 Chinese hyperphenylalanin emia cases. A single base transition 508G --> A on the DHPR cDNA was identi fied in two consanguineous DHPR-deficient siblings. A reduced level of DHPR mRNA expression was found in the other DHPR-deficient patient, which sugge sted 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 t han in Caucasian populations (1.5-2% of HPA). (C) 2001 Elsevier Science B.V . All rights reserved.