title: Demographics, diagnosis and treatment of 256 patients with tetrahydrobiopterin deficiency in mainland China: results of a retrospective, multicentre study.
abstract: BACKGROUND
  National coverage of neonatal screening for hyperphenylalaninaemia (HPA) in China is still low and tests to differentiate causes of HPA are not performed in many centres. This study aimed to describe the demographics, geographic distribution, diagnosis, treatment and clinical outcomes of treatment, including intellectual development, in patients with tetrahydrobiopterin (BH4) deficiency in mainland China.
  
  
  METHODS
  This was a retrospective, multicentre, chart review in patients with BH4 deficiency across mainland China born 1985-2010.
  
  
  RESULTS
  Two hundred fifty six patients were included; 59.9 % (267/446) of parents were from eastern China. Median (interquartile range) age at diagnosis decreased from 12.0 (5.5, 102.0) months to 2.0 (1.0, 3.5) months in patients born 1985-1999 (n = 28) and 2005-2010 (n = 152), respectively. 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. Most patients (83.6 %) received treatment with BH4, L-dopa, 5-hydroxytryptophan and/or diet therapy. Target blood Phe concentration was confirmed at 88.9 % of visits; median (Q1, Q3) blood Phe concentration was 106.8 (73.0, 120.0) μmol/L during therapy and 117.0 (67.1, 120.0) μmol/L at last visit. Median (Q1, Q3) WISC IQ score was 80.0 (69.0, 90.0) in 33 patients. DQ scores were within normal range (≥85) for 37/59 (62.7 %) patients. Physical development indicators were within normal ranges. Treatment-related adverse events, reported in 20/256 (7.8 %) patients, were mild-to-moderate in severity.
  
  
  CONCLUSIONS
  This study provides valuable information on the current and historical situation of BH4 deficiency in mainland China.
authors.affiliation: Xinhua Hospital affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.forename: Weimin
authors.initials: W
authors.lastname: Yu
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
authors.forename: Jianhui
authors.initials: J
authors.lastname: Jiang
authors.forename: Rulai
authors.initials: R
authors.lastname: Yang
authors.forename: Sunny
authors.initials: S
authors.lastname: Shang
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D019761:Phosphorus-Oxygen Lyases / Q000097:blood / Q000172:deficiency / Q000187:drug effects / Q000235:genetics; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D010649:Phenylalanine; D019761:Phosphorus-Oxygen Lyases