6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency was the primary cause of BH4 deficiency (96.0 %); four hotspot mutations accounted for 76.6 % of PTS gene mutations; two novel variants in the QDPR gene were identified.
The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles.
Autosomal recessive mutations in the 6-pyruvoyltetrahydropterin synthase (PTPS) gene are the most common reason for hyperphenylalaninemia due to tetrahydrobiopterin deficiency.