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

Carvalho, Nara de Oliveira; Castillo, Dora Méndez del; Januário, José Nélio; Starling, Ana Lúcia Pimenta; Arantes, Rodrigo Rezende; Norton, Rocksane de Carvalho; Viana, Marcos Borato

doi:10.1002/ajmg.a.61137

Cited by 11 publications

(9 citation statements)

References 19 publications

(26 reference statements)

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“…Several studies from literature suggest screening of newborn as a method of preliminary screening against several diseases. 16 During a period of 4 years, 1,066,888 newborns were screened in the state of Brazil for biotinidase deficiency, which led to the identification of nine novel mutations in 14 newborns. 17 In a study from China, 437, 342 newborn infants underwent Congenital Hypothyroidism screening.…”

Section: Discussionmentioning

confidence: 99%

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Alfadhel

Umair

Almuzzaini

et al. 2019

Ann Clin Transl Neurol

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BackgroundBiotin–thiamine‐responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement.MethodsBTBGD is a treatable disease if diagnosed at an early age and has been frequently reported in Saudi population. Keeping this in mind, the current study screened 3000 Saudi newborns for the SLC19A3 gene mutations using target sequencing, aiming to determine the carrier frequency in Saudi Population and whether BTBGD is a good candidate to be included in the newborn‐screened disorders.ResultsUsing targeted gene sequencing, DNA from 3000 newborns Saudi was screened for the SLC19A3 gene mutations using standard methods. Screening of the SLC19A3 gene revealed a previously reported heterozygous missense mutation (c.1264A>G (p.Thr422Ala) in six unrelated newborns. No probands having homozygous pathogenic mutations were found in the studied cohort. The variant has been frequently reported previously in homozygous state in Saudi population, making it a hot spot mutation. The current study showed that the carrier frequency of SLC19A3 gene mutation is 1 of 500 in Saudi newborns.ConclusionFor the first time in the literature, we determined the carrier frequency of SLC19A3 gene mutation in Saudi population. The estimated prevalence is too rare in Saudi population (at least one in million); therefore, the data are not in favor of including such very rare disorders in newborn screening program at population level. However, a larger cohort is needed for a more accurate estimate.

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Section: Discussionmentioning

confidence: 99%

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Alfadhel

Umair

Almuzzaini

et al. 2019

Ann Clin Transl Neurol

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“…Further, 11 novel variants were detected by our group. 8,18 These observations illustrate the genetic diversity in the Brazilian population.…”

Section: Discussionmentioning

confidence: 53%

“…Eight alleles were excluded because they were found in siblings. Parental BTD sequencing was done for only 16 Novel variants are those cited in the reference Carvalho (2019) 18 .…”

Section: Resultsmentioning

confidence: 99%

Frequency of biotinidase gene variants and incidence of biotinidase deficiency in the Newborn Screening Program in Minas Gerais, Brazil

et al. 2019

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Objective The prevalence of biotinidase deficiency and the frequency of biotinidase gene variants in Brazil are not documented. We aimed to determine the incidence of partial and profound biotinidase deficiency in the state of Minas Gerais, Brazil, and to calculate the frequency of biotinidase gene variants in the newborn screening program of Minas Gerais. Methods Neonates (1,168,385) were screened from May 2013 to June 2018. Those detected with abnormal biotinidase activity based on semi-quantitative assays underwent confirmatory serum tests. The biotinidase gene was sequenced in all confirmed cases. Results The combined incidence of partial and profound biotinidase deficiency was estimated at 1:13,909 live births (95% confidence limit 1:11,235–1:17,217), much higher than the incidence rates reported in other populations worldwide. The most frequent biotinidase gene variants were p.D444H (allele frequency, 0.016), haplotype c.1330G>C;c.511G>A (p.D444H;A171T), p.D543E, c.310-15delT (intronic), p.V199M, and p.H485Q. Together these accounted for 74.6% of the alleles analysed. Conclusion Newborn screening for biotinidase deficiency, which revealed a higher incidence in Minas Gerais, is feasible and plays a critical role in the early identification of affected neonates and prevention of symptoms and irreversible sequelae. Biotinidase gene sequencing is a useful tool to confirm the diagnosis, and also provides valuable information about genetic variability among different populations.

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“…A recent report from the Czech Republic showed successful confirmed diagnosis of 21 BTD patients out of 181,396 screened neonates in the period from June 2017 to end of 2017 [29]. In Minas Gerais state in Brazil, a newborn screening program tested over one million neonates for BTD since it was introduced to the program in 2013, with novel variants identified in 14 patients [30].…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of BTD Gene Mutations in Jordanian Children with Biotinidase Deficiency

AL-Eitan

Alqa'qa'

Amayreh

et al. 2020

JPM

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Biotinidase deficiency is an autosomal recessive metabolic disorder whose diagnosis currently depends on clinical symptoms and a biotinidase enzyme assay. This study aimed to investigate the mutational status and enzymatic activity of biotinidase deficiency in seven unrelated Jordanian families including 10 patients and 17 healthy family members. Amplified DNA was analyzed by the automated Sanger sequencing method, and the enzymatic assay was performed using a colorimetric assessment. Biotinidase level was significantly lower (p < 0.001) in BTD children compare to their non-affected family members. Genetic sequencing revealed six different mutations in Jordanian patients. One mutation was novel and located in exon 4, which could be a prevalent mutation for biotinidase deficiency in the Jordanian population. Identification of these common mutations and combing the enzymatic activity with genotypic data will help clinicians with regard to better genetic counseling and management through implementing prevention programs in the future.

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

Cited by 11 publications

References 19 publications

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening

Frequency of biotinidase gene variants and incidence of biotinidase deficiency in the Newborn Screening Program in Minas Gerais, Brazil

Identification and Characterization of BTD Gene Mutations in Jordanian Children with Biotinidase Deficiency

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