title: High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in Minas Gerais, Brazil.
abstract: OBJECTIVE
  To assess the incidence of biotinidase deficiency among newborns and their clinical outcome up to one year of age in a large pilot screening study in Minas Gerais, Brazil.
  
  
  METHODS
  A prospective cohort study was conducted from September 2007 to June 2008 with heel-prick blood samples collected on filter paper for the purpose of newborn screening. A qualitative colorimetric test was used as the primary screening method. Colorimetric-positive cases were further tested with a serum confirmatory assay. Gene sequencing was performed for eight children suspected with biotinidase deficiency and for some of their parents. Positive cases were daily supplemented with oral biotin and were followed up for approximately six years.
  
  
  RESULTS
  Out of 182,891 newborns screened, 129 were suspected of having biotinidase deficiency. Partial deficiency was confirmed in seven children (one was homozygous for p.D543E) and profound deficiency in one child (homozygous p.H485Q). Thus the incidence was one in 22,861 live births (95% confidence interval 1:13,503 to 1:74,454) for profound and partial biotinidase deficiency combined. Two novel mutations were detected: p.A281V and p.E177K. In silico analysis and estimation of the enzyme activity in the children and their parents showed that p.A281V is pathogenic and p.E177K behaves like p.D444H.
  
  
  CONCLUSIONS
  The incidence of biotinidase deficiency in newborn screening in Minas Gerais was higher than several international studies. The sample size should be larger for final conclusions. Oral daily biotin apparently precluded clinical symptoms, but it may have been unnecessary in some newborns.
authors.affiliation: UFMG University Hospital, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marilis T
authors.initials: MT
authors.lastname: Lara
authors.affiliation: Department of Pediatrics, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Gurgel-Giannetti
authors.affiliation: Department of Pediatrics, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marcos J B
authors.initials: MJ
authors.lastname: Aguiar
authors.affiliation: NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Roberto V P
authors.initials: RV
authors.lastname: Ladeira
authors.affiliation: NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Nara O
authors.initials: NO
authors.lastname: Carvalho
authors.affiliation: NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Dora M
authors.initials: DM
authors.lastname: Del Castillo
authors.affiliation: Department of Pediatrics, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marcos B
authors.initials: MB
authors.lastname: Viana
authors.affiliation: Department of Medicine, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Av. Alfredo Balena 189, sala 1004, 30130-100, Belo Horizonte, Brazil. nelio@nupad.medicina.ufmg.br.
authors.forename: José N
authors.initials: JN
authors.lastname: Januario
keywords: Biotin; Biotinidase deficiency; Gene sequencing; Neonatal screening