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. Colorimetricpositive 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.

Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil

“…Patient #3 was partially enzyme‐deficient, his father's enzyme activity was suggestive of heterozygosis, and his mother's enzyme activity was in the borderline of the heterozygote/normal range. Hence, the p.S311 T mutation may be a mildly pathogenic variant, functionally similar to p.D444H and E177K (c.529G > A), as previously reported by our group (Lara et al, ). In silico programs, however, predict that p.S311 T is pathogenic or probably pathogenic (Table ).…”

“…Mutation analyses were performed as previously described in the pilot study that preceded the implementation of the newborn program for BTD deficiency (Lara et al, ).…”

Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics

“…[52][53][54] Currently, all newborn screening programs in the United States and more than 30 other countries screen for biotinidase deficiency, with multiple recent studies suggesting that additional countries are considering incorporation of biotinidase deficiency into their newborn screening programs. [55][56][57][58][59][60] Historically, the screening method used was a colorimetric assay of biotinidase activity measured in dried blood spots, and states have individually established their own screening cutoffs and rescreening or follow-up protocols. 50 Commercial kits based on fluorescence are now available, and at this time no data are available regarding the frequency of use of the different assays across the United States.…”

Clinical utility gene card for: Biotinidase deficiency—update 2015

“…This question coincides with the debate over the usefulness of programmes of newborn screening of biotinidase deficiency based on measurement of biotinidase enzyme activity. One can distinguish between two categories of countries: those which chose to develop a systematic newborn screening programme for early diagnosis of biotinidase deficiency, such as the USA, 29 some European countries, 16 Turkey 30 or Brazil, 31 and those which did not choose such an option and preferred to rely on clinical diagnosis to identify affected individuals. From an economical perspective, the choice of one option over the other is guided by the balance between the overall cost of a massive screening involving thousands of newborns per year and the cost of more complex medical healthcare regarding much fewer infants clinically diagnosed with biotinidase deficiency.…”