Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey

Yılmaz, Bilge; Mungan, Neslihan Önenli; Kör, Deniz; Bulut, Derya; Seydaoğlu, Gülşah; Öktem, M.; Ceylaner, Serdar

doi:10.1515/jpem-2017-0406

Cited by 13 publications

(10 citation statements)

References 19 publications

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“…Our genetic data confirmed that partial BD are more frequent than profound (88.1%) and are characterized by a distinctive genotype with a high prevalence of the c.1330G>C (p.Asp444His) variant (8,19). Essentially, all individuals with partial BD have the mutation c.1330G>C (p.Asp444His) in one or both alleles of the BTD gene in combination with a mutation associated with profound BD in heterozygosity, and this is in agreement with other studies already reported in the literature (10,14,16,21).…”

Section: Discussionsupporting

confidence: 91%

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

et al. 2021

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Introduction: Biotinidase deficiency (BD) is an autosomal recessive disease causing a defect in the biotin-releasing enzyme. Newborn screening (NBS) allows early diagnosis and treatment, ensuring excellent prognosis. The aim of this study was to describe our experience in the diagnosis, treatment, and follow-up showing key strategies and unsolved questions of the management of BD patients.Methods: We analyzed data of patients identified by the Regional Centre for Newborn Screening of Verona and followed by the Inherited Metabolic Disease Unit of Verona and Neonatal Intensive Care Unit of Bolzano, Italy, from 2014 to 2020.Results: Thirty-seven patients were diagnosed by NBS (five profound and 32 partial BD), with a total incidence of 1:5,996. All were started on biotin at diagnosis and presented no symptoms at follow-up. Analysis of parents and siblings led to identification of five asymptomatic patients with partial BD: one asymptomatic parent and four young siblings. Genetic analysis of the BTD gene identified 17 different genotypes and one mutation not previously known.Discussion: Our data confirm that NBS introduction had a dramatic impact on BD diagnosis, and the incidence has increased significantly compared to other areas. Partial defects are more common than profound and have a distinctive genotype. Partial BD treatment is still controversial even at what dose of biotin and for how long. At the end, BD treatment is very easy and inexpensive and prevents severe neurological damage. Sharing experiences is essential to achieving guidelines for treatment and follow-up and a better genotype–phenotype correlation.

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Section: Discussionsupporting

confidence: 91%

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

et al. 2021

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“…In most previous studies, a higher frequency of profound and partial BTD forms was reported in the literature (5,20,21). The frequency of profound BTD determined based on the rst test results of this study was found to be similar to (8.2%) these previous reports.…”

Section: Discussionsupporting

confidence: 85%

“…This study reveals long-term follow-up consequences for patients diagnosed with BTD. Most of the reports related to BTD are crosssectional studies, and they involve the neonatal or early infant period (5,8,20). Most previous evaluations were performed with single measurement results, while the present study reports the long-term consequences of genotype-phenotype association with the change in consecutive biotinidase enzyme activity results.…”

Section: Discussionmentioning

confidence: 79%

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The Course of Biotinidase Activities After Neonatal Period in The Screened Newborns and Consequences of The Concordance With Their Genotypes.

Karaoğlan

Nacarkahya

Aytaç

et al. 2021

Preprint

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Background/aim: Biotinidase deficiency (BTD) is characterized by broad genotypic variants and unsteady biotinidase activity. Increasing enzyme activity and maturation throughout childhood. This study aims to reveal the course of biotinidase activities in a long-term follow-up period and concordance with their genotypes .Participants/Methods: A total of 1,773 biotinidase enzyme (BT) activity measurements were performed in 711 newborns with variants in the BTD gene over a 4-year follow-up period. Biochemical phenotyping was classified into four groups based on the highest measured enzyme activity level during the follow-up: Profound(≤10%), Partial(10.1-30%), Heterozygous(30.1-66.5%), and Normal(>66.6%). Results: The number of participants with BTD in the biochemical phenotype groups assigned based on the first measurement was 59, 217, 314, and 121 in the profound, partial, heterozygous, and normal groups respectively. Based on the highest measurement value during follow-up, the number and net changes of participants in groups were 22(-37), 95(-122), 333(+19), and 261(+140), respectively. The overall concordance between genotypes and biotinidase activities based on the highest measurement was 50.7%. A moderate correlation was found between the highest enzyme value and age (r=-0.573, p=0.002) in heterozygous plus normal biochemical phenotype groups in first months.Conclusion:This study shows that the biotinidase activities increase at a later age after neonatal period during long-term follow-up, and there is low concordance between the biochemical phenotype and their genotype. These findings indicate the important role of the monitoring the course of biotinidase enzyme activities for a longer period of time to determine the treatment decision.

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“…8 In an unpublished study conducted at our centre in newborns who were referred from the National Biotinidase Screening Program, the carrier incidence for BTD was determined to be 1:1155. Biochemical phenotypes are classified into two or four biochemical groups based on normal enzyme activity values 9,10 : profound (<10% of normal enzyme activity), partial (10.1%-30%), heterozygous (30.1%-66.5%) and normal (higher than 66.6%). It has been reported that the degree of multiple carboxylases and biotinidase enzyme activity are good indicators of the status of biotin deficiency.…”

Section: Introductionmentioning

confidence: 99%

Immunophenotypic analysis of lymphocyte subsets in newborns with biotinidase deficiency

Karaoğlan

Nacarkahya

Keskın

et al. 2020

Pediatric Allergy Immunology

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Background/Aim: Biotin is a vital micronutrient that plays a role in metabolic homeostasis and the regulation of innate and adaptive immune system functions. Biotinidase deficiency (BTD) leads to impairment in biotin-dependent immune functions. This study focused on immunophenotypic analysis of lymphocyte subsets in newborns with BTD. Patients and Methods: A total of 181 (95 female and 86 male; 114 had BTD and 67 were healthy) newborns underwent biotinidase enzyme activity, molecular and lymphocyte immunophenotyping analyses. BTD is classified into four biochemical phenotypes: profound, partial, heterozygous and normal. The following lymphocyte subsets were studied in all participants: total B lymphocyte (CD19), total T lymphocyte (CD3), helper T lymphocyte (CD3/CD4), cytotoxic T lymphocyte (CTL) (CD3/ CD8), natural killer T lymphocyte (CD16/56) and a T-lymphocyte activation marker (HLA-DR). Results: The percentages of lymphocyte subsets were similar in newborns with and without BTD. In all newborns with BTD, the mean CD3/CD4 levels were higher in females, while the CD3/CD8 levels were higher in males (P < .001 for each). In female and male newborns, the CD3/CD4 levels were 53.83 ± 9.46 and 16.82 ± 5.19, respectively, and the CD3/CD8 levels were 48.80 ± 8.65 and 21.48 ± 6.02, respectively. A moderate negative correlation was found between CD3/CD4 and CD3/CD8 in female and male newborns (r female = −0.488, r male = −0.574, P < .001). Conclusion: This study showed that although there were no differences in the lymphocyte subsets in newborns with BTD, the CD3/CD4 levels were higher in females, and the CD3/CD8 levels were higher in males. In addition, there was a negative correlation between the CD3/CD4 and CD3/CD8 levels in both genders. Although these results indicate sexual dimorphism between CD3/CD4 and CD3/CD8 levels, whether this dissociation is unique to BTD in newborns is not fully clear.

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Twenty-seven mutations with three novel pathologenic variants causing biotinidase deficiency: a report of 203 patients from the southeastern part of Turkey

Abstract: We determined the mutation spectra of BD from the southeastern part of Turkey. The results of this study add three more mutations to the total number of mutations described as causing BD.

Cited by 13 publications

References 19 publications

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

Newborn Screening for Biotinidase Deficiency. The Experience of a Regional Center in Italy

The Course of Biotinidase Activities After Neonatal Period in The Screened Newborns and Consequences of The Concordance With Their Genotypes.

Immunophenotypic analysis of lymphocyte subsets in newborns with biotinidase deficiency

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