[Studies on neonatal screening, clinical and gene analysis for tetrahydrobiopterin deficiency in Southern Chinese]

To find out the incidence of tetrahydrobiopterin deficiency(BH4D) among patients with hyperphenylalaninemia in Southern Chinese and evaluate the clinical outcome and gene mutations of tetrahydrobiopterin deficient patients.

Analyses of urinary neopterin(N) and biopterin(B) were done in 87 patients with hyperphenylalaninemia by high-performance liquid chromatography. The patients with BH4 deficiency and their parents were asked to undergo the gene mutation analysis and the patients were treated and followed up.

Eleven cases of which the urinary N/B ratio was higher than 38 and B% lower than 5% were diagnosed as BH4 deficiency caused by 6-pyruvoyl-tetrahydropterin synthase(PTPS) deficiency. The incidence of BH4 deficiency among patients with hyperphenylalaninemia is 12% in Southern Chinese. PTPS gene mutations (P87S, N52S, D96N and G144R) were detected from 5 PTPS deficient families. The G144R mutation is a new mutation. The five PTPS-deficient patients were treated with synthetic BH4, neurotransmitter precursors L-dopa and 5-hydroxytryptophan. They had satisfactory physical and mental development after treatment, and 4 of them scored their IQ 70-80.

The screening for BH4 deficiency should be carried out in all patients with hyperphenylalaninemia in order to minimize the misdiagnoses.