[Screening for tetrahydrobiopterin metabolic disorders and related gene analysis among the patients with motor disturbance and mental retardation].
OBJECTIVE
To study the incidence of various enzyme deficiency in tetrahydrobiopterin (BH4) metabolism and the related gene mutation among the patients with motor disturbance and mental retardation.


METHODS
One hundred patients with unknown motor disturbance and mental retardation were referred to this study. All patients were performed by phenylalanine (Phe) and BH4 loading test, urinary pterin analysis and dihydropteridine reductase (DHPR) activity. Some patients received the dopa treatment for diagnosis of dopa-responsive dystonia (DRD). The analysis of GTP cyclohydrolase 1 gene (GCH1) mutation for DRD patients and the analysis of 6-pyruvoyl tetrahydropterin synthase (PTS) gene mutations for PTS deficient patients were done under the consent from their parents.


RESULTS
Seventy of 100 patients had normal basic blood Phe levels, six (6%) patients were diagnosed as DRD. Thirty patients had hyperphenylalaninemia (HPA), eight (8%) were diagnosed as PTS deficiency and 22(22%) were diagnosed as phenylalanine hydroxylase (PAH) deficiency. All patients had normal DHPR activity. The mutation IVS5+3insT of GCH1 was found in 2 patients with DRD. Seven kinds of PTS mutations were found in 8 patients with PTS deficiency, and 75% of the mutations were 259C-->T,286G-->A and 155A-->G.


CONCLUSIONS
Some patients with unknown motor disturbance and mental retardation may suffer from BH4 metabolism related diseases. Theses patients are necessary to be screened for such kind of diseases in order to confirm the diagnosis.
Ye
Jun
J
Affiliated Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai, 200092 PR China.
Liu
Xiao-qing
XQ
Qiu
Wen-juan
WJ
Han
Lian-shu
LS
Zhou
Jian-de
JD
Zhang
Ya-fen
YF
Gu
Xue-fan
XF
D000293:Adolescent; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004093:Dihydropteridine Reductase / Q000235:genetics / Q000378:metabolism; D004421:Dystonia / Q000235:genetics / Q000378:metabolism; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism
D001708:Biopterins; D010651:Phenylalanine Hydroxylase; D004093:Dihydropteridine Reductase; D006136:GTP Cyclohydrolase; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin