Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations.
Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. 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. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.
Chien
Y H
YH
Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.
Chiang
S C
SC
Huang
A
A
Lin
J M
JM
Chiu
Y N
YN
Chou
S P
SP
Chu
S Y
SY
Wang
T R
TR
Hwu
W L
WL
D006916:5-Hydroxytryptophan / Q000627:therapeutic use; D001483:Base Sequence; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D018703:Founder Effect; D006801:Humans; D007231:Infant, Newborn; D007360:Intelligence; D007980:Levodopa / Q000627:therapeutic use; D009154:Mutation; D015997:Neonatal Screening; D010649:Phenylalanine / Q000008:administration & dosage / Q000097:blood; D010661:Phenylketonurias / Q000201:enzymology* / Q000235:genetics* / Q000523:psychology / Q000628:therapy; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics*; D013624:Taiwan; D016896:Treatment Outcome
D001708:Biopterins; D007980:Levodopa; D010649:Phenylalanine; D006916:5-Hydroxytryptophan; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin