SCREENING FOR TETRAHYDROBIOPTERIN
DEFICIENCY AMONG HYPERPHENYLALANINEMIA IN SOUTHERN CHINESE
Ye J, Gu XF, Liu XQ, Huang XD
Xin Hua Hospital, Shanghai
Second Medical University and Shanghai Institute for Pediatric Research,
Shanghai, China
Objective: To
find the incidence of tetrahydrobiopterin deficiency (BH4D) among patients
with hyperphenylalaninemia(HPA) in Southern Chinese and evaluate the
clinical outcome and gene mutations in BH4D
Methods: Analysis of urinary
neopterin (N) and biopterin (B) was done in 87 patients with HPA by HPLC.
Further combined loading test with phenylalanine and tetrahydrobiopterin
were performed in suspected cases with abnormal urinary pterin profiles.
Gene mutation analysis was performed for BH4D patients.
Results: Eleven patients were diagnosed as having BH4
deficiency caused by 6-Pyruvoyl tetrahydropterin synthase (PTPS)
deficiency. The six PTPS- deficient patients were found in 50 PKU diagnosed
by neonatal screening in Southern Chinese, with the incidence of BH4 deficiency
of 12%. The Phe levels were decreased to normal 4-6h after BH4
administration in 4 of 11 patients. Four different mutations (P87S, N52S,
D96N and G144R) in PTPS gene were detected from 5 families. The five
PTPS-deficient patients had satisfactory physical and mental development
after treatment with synthetic BH4, neurotransmitter precursors Dopa and
5-hydroxytryptophan.
Conclusions: Our results emphasize that screening for BH4
deficiency should be carried out in all patients with hyperphenylalaninemia
in order to minimize the misdiagnoses.