Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014)

Srinitya Gannavarapu, Chitra Prasad, Jennifer DiRaimo, Melanie Napier, Sharan Goobie, Murray Potter, Pranesh Chakraborty, Maria Karaceper, Tatiana Munoz, Andreas Schulze, Jennifer MacKenzie, Lihua Li, Michael T. Geraghty, Osama Y. Al-Dirbashi, C. Anthony Rupar

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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 8. years. 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.

Original languageEnglish
Pages (from-to)146-151
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number3
StatePublished - Nov 2015
Externally publishedYes


  • Biochemical phenotype-genotype associations
  • Biotinidase deficiency
  • Metabolic disease
  • Mutation analysis
  • Newborn screening


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