Marilis T Lara1, Juliana Gurgel-Giannetti2, Marcos J B Aguiar2, Roberto V P Ladeira3, Nara O Carvalho3, Dora M Del Castillo3, Marcos B Viana2, José N Januario4. 1. UFMG University Hospital, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil. 2. Department of Pediatrics, NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil. 3. NUPAD - Center for Newborn Screening and Genetic Diagnostics, UFMG Federal University of Minas Gerais, Belo Horizonte, Brazil. 4. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Barry Wolf; Kevin P Jensen; Bruce Barshop; Miriam Blitzer; Martha Carlson; David R Goudie; Gulden Huner Gokcay; Mubeccel Demirkol; Tolunay Baykal; F Demir; Sharon Quary; Ling Yu Shih; Helio F Pedro; Tsui-Hua H Chen; Alfred E Slonim Journal: Hum Mutat Date: 2005-04 Impact factor: 4.878
Authors: J R McVoy; H L Levy; M Lawler; M A Schmidt; D D Ebers; P S Hart; D D Pettit; M G Blitzer; B Wolf Journal: J Pediatr Date: 1990-01 Impact factor: 4.406
Authors: K Sarafoglou; K Bentler; A Gaviglio; K Redlinger-Grosse; C Anderson; M McCann; B Bloom; D Babovic-Vuksanovic; D Gavrilov; S A Berry Journal: J Inherit Metab Dis Date: 2009-09-07 Impact factor: 4.982
Authors: K L Swango; M Demirkol; G Hüner; E Pronicka; J Sykut-Cegielska; A Schulze; E Mayatepek; B Wolf Journal: Hum Genet Date: 1998-05 Impact factor: 4.132
Authors: Taciane Borsatto; Fernanda Sperb-Ludwig; Louise L C Pinto; Gisele R De Luca; Francisca L Carvalho; Carolina F M De Souza; Paula F V De Medeiros; Charles M Lourenço; Reinaldo Lo Filho; Eurico C Neto; Pricila Bernardi; Sandra Leistner-Segal; Ida V Schwartz Journal: BMC Med Genet Date: 2014-09-01 Impact factor: 2.103
Authors: Daniela Semeraro; Sara Verrocchio; Giulia Di Dalmazi; Claudia Rossi; Damiana Pieragostino; Ilaria Cicalini; Rossella Ferrante; Silvia Di Michele; Liborio Stuppia; Cristiano Rizzo; Francesca Romana Lepri; Antonio Novelli; Carlo Dionisi-Vici; Vincenzo De Laurenzi; Ines Bucci Journal: Int J Environ Res Public Health Date: 2022-07-02 Impact factor: 4.614
Authors: Taciane Borsatto; Fernanda Sperb-Ludwig; Samyra E Lima; Maria R S Carvalho; Pablo A S Fonseca; José S Camelo; Erlane M Ribeiro; Paula F V de Medeiros; Charles M Lourenço; Carolina F M de Souza; Raquel Boy; Têmis M Félix; Camila M Bittar; Louise L C Pinto; Eurico C Neto; Henk J Blom; Ida V D Schwartz Journal: PLoS One Date: 2017-05-12 Impact factor: 3.240
Authors: Ilaria Cicalini; Damiana Pieragostino; Cristiano Rizzo; Sara Verrocchio; Daniela Semeraro; Mirco Zucchelli; Silvia Di Michele; Carlo Dionisi-Vici; Liborio Stuppia; Vincenzo De Laurenzi; Ines Bucci; Claudia Rossi Journal: Int J Environ Res Public Health Date: 2021-02-09 Impact factor: 3.390