title: [Diagnosis and treatment of biotinidase deficiency-clinical study of six patients].
abstract: OBJECTIVE
  To investigate the clinical and neurodevelopmental profiles of patients with biotinidase deficiency and to determine the efficacy of current therapy with respect to outcome.
  
  
  METHODS
  Six patients aged from 3 months to 14 years with biotinidase deficiency were confirmed by urinary organic acid analysis with gas chromatography/mass spectrometry (GC/MS) and biotinidase assay on dried blood spots. Biotin was supplemented individually (10-40 mg/d). Their clinical features, laboratory findings, and treatment regimen were reviewed.
  
  
  RESULTS
  All the 6 patients presented with some extent of neurological abnormalities and dermatological lesions. Cases 1 - 3 had poor feeding, vomiting, seizures, mental retardation, and lethargy onset from their early infancy, with varied degree of anemia, ketosis, acidosis, and hypoglycemia. Case 2 exhibited eczema and dermatitis from his age of 7 months. Case 4 displayed motor deficit and ataxia after 6 months of age, and generalized pustular psoriasis when he was 8 months old. Cases 5 and 6 gradually showed muscle weakness and paraplegia at the age of 7 years and 5 years, respectively. Inflammatory demyelination changes of cervical cord were evident on magnetic resonance imaging in these two patients. Case 6 had progressive optic atrophy, eczema and alopecia. Remarkable elevations of urinary lactate, pyruvate, 3-OH-propionate, methylcitrate, propionylglycine, 3-OH-isovalerate, 3-methylcrontonylglycine were confirmed in cases 1, 2, 3 and 5. Slight increase of urinary lactate, pyruvate, and 3-methylcrontonylglycine was observed in cases 4 and 6. Biotinidase activities assayed on dried blood spots from all the patients were below 0.1 pmol/(min.3 mm) Biotin supplementation for all the patients, except for case 3 who was not treated, resulted in pronounced and rapid clinical and biochemical improvement. Cases 4 and 6 had residual neurological damage comprising ataxia and motor handicap of legs, due to prolonged disease course.
  
  
  CONCLUSIONS
  Biotinidase deficiency intensively impairs nervous system and skin in the affected patients. Urinary organic acid analysis and blood biotinidase assay are crucial to the diagnosis. Early diagnosis and biotin supplementation can contribute significantly to the improvement of prognosis.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tagami
authors.forename: Yue-hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Xiong
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kimura
authors.forename: Junji
authors.initials: J
authors.lastname: Hanai
authors.forename: Kozo
authors.initials: K
authors.lastname: Fujita
authors.forename: Ning
authors.initials: N
authors.lastname: Qian
authors.forename: Xiao-ju
authors.initials: XJ
authors.lastname: He
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Bao
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D001710:Biotin / Q000008:administration & dosage / Q000627:therapeutic use*; D028921:Biotinidase Deficiency / Q000175:diagnosis* / Q000188:drug therapy* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D008297:Male; D016896:Treatment Outcome
chemical_list: D001710:Biotin