title: Diagnosis, treatment, follow-up and gene mutation analysis in four Chinese children with biotinidase deficiency.
abstract: OBJECTIVE
  To report the clinical course and explore the gene mutation spectrum of four Chinese children with biotinidase deficiency.
  
  
  METHODS
  Four Chinese patients aged 4 months to 8 years were referred to this study. Tandem mass spectrometry, gas chromatography-mass spectrometry and the determination of biotinidase activities were performed for selective screening of biotinidase deficiency. Four patients with biotinidase deficiency were diagnosed, treated with biotin and followed.
  
  
  RESULTS
  (1) Four patients with biotinidase deficiency were diagnosed by characteristic metabolites, such as elevated blood levels of 3-hydroxyisovalerylcarnitine (6.22 +/- 3.1 mumol/L), elevated 3-methylcrontonylglycine, methylcitrate and 3-hydroxypropionate in urine and very low biotinidase activities. (2) These patients have been treated with biotin for 1-8 years; two of them still have mental retardation, and two have irreversible hearing or vision disability. (3) In the four patients, six different mutations in the biotinidase gene were identified: c.98G:del7ins3, c.1369G>A (p. V457M), c.1384delA, c.1493_1494insT, c.1284C>A (p.Y428X) and c.1157G>A (p.W386X). The latter four mutations are novel variations. Seven out of eight mutations are located on exon 4 of the biotinidase gene.
  
  
  CONCLUSIONS
  Early recognition of biotinidase deficiency is crucial to avoid permanent damage. Determination of biotinidase activity should be included in neonatal screening in China. Exon 4 may be a hot-spot for biotinidase gene mutations in Chinese patients. Four novel gene variations may be disease-causing mutations and should be confirmed by expression studies.
authors.affiliation: Department of Pediatric Endocrinology and Genetic Metabolism, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665 Kong Jiang Road, Shanghai, 200092, China.
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: L S
authors.initials: LS
authors.lastname: Han
authors.forename: W J
authors.initials: WJ
authors.lastname: Qiu
authors.forename: H W
authors.initials: HW
authors.lastname: Zhang
authors.forename: Y F
authors.initials: YF
authors.lastname: Zhang
authors.forename: X L
authors.initials: XL
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: X F
authors.initials: XF
authors.lastname: Gu
mesh_terms: D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D001710:Biotin / Q000627:therapeutic use; D043523:Biotinidase / Q000235:genetics*; D028921:Biotinidase Deficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening
chemical_list: D001710:Biotin; D043523:Biotinidase