title: Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014).
abstract: Untreated profound biotinidase deficiency results in a wide range of clinical features, including optic atrophy, cutaneous abnormalities, hearing loss and developmental delay. Ontario, Canada incorporated this treatable deficiency in newborn screening over the past 8years. This study elucidates the molecular, biochemical, and clinical findings from the pilot project. Information from initial screens, serum biotinidase activity level assays, molecular testing, and family history for 246 positive newborns screens were analyzed. A mutation spectrum was created for the province of Ontario, including common mutations such as D444H, D444H/A171T, Q456H, C33fs, and R157H. Individuals with partial deficiency were separated into 3 groups: D444H homozygotes (Group 1); compound heterozygotes for D444H with another profound allele (Group 2); compound heterozygotes with two non-D444H alleles (Group 3). Biochemical phenotype-genotype associations in partial deficiency showed a significant difference in serum biotinidase activity in between any given two groups. Three children with partial deficiency discontinued biotin for varied lengths of time. Two of whom became symptomatic with abnormal gait, alopecia, skin rashes and developmental delay. A need for more congruency in diagnostic, treatment and educational practices was highlighted across the province. Heterogeneity and variation in clinical presentations and management was observed in patients with the partial deficiency.
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada.
authors.forename: Srinitya
authors.initials: S
authors.lastname: Gannavarapu
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada. Electronic address: Chitra.Prasad@lhsc.on.ca.
authors.forename: Chitra
authors.initials: C
authors.lastname: Prasad
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: DiRaimo
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Napier
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada.
authors.forename: Sharan
authors.initials: S
authors.lastname: Goobie
authors.affiliation: Department of Pathology and Molecular Medicine McMaster University, Hamilton ON, Canada.
authors.forename: Murray
authors.initials: M
authors.lastname: Potter
authors.affiliation: Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa ON, Canada.
authors.forename: Pranesh
authors.initials: P
authors.lastname: Chakraborty
authors.affiliation: Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa ON, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Karaceper
authors.affiliation: Divison of Clinical and Metabolic Genetics, Department of Pediatrics, the Hospital for Sick Children and University of Toronto, ON, Canada.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Munoz
authors.affiliation: Divison of Clinical and Metabolic Genetics, Department of Pediatrics, the Hospital for Sick Children and University of Toronto, ON, Canada; Genetics and Genome Biology, Peter Gilgan Centre for Research and Learning, the Hospital for Sick Children, Toronto ON, Canada.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Department of Pediatrics, Queen's University, Kingston ON, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: MacKenzie
authors.affiliation: Division of Nephrology, Department of Medicine, Western University, London ON, Canada.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa ON, Canada; Division of Metabolics, Department Pediatrics, University of Ottawa, ON, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Geraghty
authors.affiliation: Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa ON, Canada; Division of Metabolics, Department Pediatrics, University of Ottawa, ON, Canada.
authors.forename: Osama Y
authors.initials: OY
authors.lastname: Al-Dirbashi
authors.affiliation: Department of Pediatrics London Health Sciences Centre and Western University, London ON, Canada; Department of Pathology and Laboratory Medicine Western University, London, ON, Canada.
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Rupar
mesh_terms: D000483:Alleles; D000581:Amidohydrolases / Q000235:genetics; D001710:Biotin / Q000627:therapeutic use; D043523:Biotinidase / Q000097:blood / Q000235:genetics; D028921:Biotinidase Deficiency / Q000175:diagnosis / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019468:Disease Management; D005260:Female; D056726:Genetic Association Studies; D034381:Hearing Loss / Q000209:etiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D009864:Ontario / Q000453:epidemiology; D010865:Pilot Projects
chemical_list: D001710:Biotin; D000581:Amidohydrolases; D043523:Biotinidase
keywords: Biochemical phenotype-genotype associations; Biotinidase deficiency; Metabolic disease; Mutation analysis; Newborn screening