Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers
Background: Biotin is the coenzyme of multiple carboxylases involved in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotinidase (BTD) deficiency is an autosomal recessive disorder affecting the biotin cycle. It disrupts endogenous biotin recycling and results in multiple carbox...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2022-01-01
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| Series: | Indian Pediatrics Case Reports |
| Subjects: | |
| Online Access: | http://www.ipcares.org/article.asp?issn=2772-5170;year=2022;volume=2;issue=1;spage=12;epage=16;aulast=Mishra |
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| author | Ranjana Mishra Meenakshi Bothra Gupta Sharmila B Mukherjee Avinash Lomash Sangeeta Gupta Seema Kapoor |
| author_facet | Ranjana Mishra Meenakshi Bothra Gupta Sharmila B Mukherjee Avinash Lomash Sangeeta Gupta Seema Kapoor |
| author_sort | Ranjana Mishra |
| collection | DOAJ |
| description | Background: Biotin is the coenzyme of multiple carboxylases involved in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotinidase (BTD) deficiency is an autosomal recessive disorder affecting the biotin cycle. It disrupts endogenous biotin recycling and results in multiple carboxylase deficiency depending upon the level of enzyme activity. Children with profound deficiency often present in infancy with neurocutaneous manifestations. Management of symptomatic children or screen-positive newborns is lifelong oral supplementation with biotin. There may be partial or complete resolution of symptoms in the former. Clinical Description: We describe two unrelated families diagnosed as profound BTD deficiency, with three affected children in each family. The first family had two symptomatic surviving children, a 2-year-old boy with seizures, developmental delay, and hearing loss, and a 1.5-month-old boy with seizures. Diagnosis was established while ascertaining etiology for seizures refractory to multiple anticonvulsant therapy. The second family was referred for postconceptional counseling following two infantile deaths with similar phenotype, early-onset seizures, encephalopathy, and acute metabolic decompensation. Management: The affected children in the first family showed a dramatic response in seizure controls with oral biotin though the other symptoms such as developmental delay and hearing loss remained unaffected. Mother was advised regarding prenatal diagnosis in the next pregnancy but was unwilling. In the second family, stored genetic material from the earlier affected infant revealed a pathogenic homozygous indel in the BTD gene, which was confirmed in utero in the subsequent pregnancy. Both women were started on oral biotin on the lines of antenatal management of holocarboxylase synthetase deficiency. After birth, therapy was continued on the confirmation of profound BTD deficiency in both babies. They have remained asymptomatic on follow-up; the first baby till a year and the second till 3 months. Conclusion: There is a considerable phenotypic variability in profound BTD deficiency. Early detection and prompt treatment with biotin may result in complete resolution of some symptoms and ameliorate others. Antenatal biotin supplementation in families at high risk or with prenatal diagnosis of BTD deficiency may have a favorable outcome in affected progeny. |
| first_indexed | 2024-04-24T19:26:45Z |
| format | Article |
| id | doaj.art-9f5d2279a3e3415fadad0b1981120860 |
| institution | Directory Open Access Journal |
| issn | 2772-5170 2772-5189 |
| language | English |
| last_indexed | 2024-04-24T19:26:45Z |
| publishDate | 2022-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Indian Pediatrics Case Reports |
| spelling | doaj.art-9f5d2279a3e3415fadad0b19811208602024-03-25T15:38:28ZengWolters Kluwer Medknow PublicationsIndian Pediatrics Case Reports2772-51702772-51892022-01-0121121610.4103/ipcares.ipcares_12_22Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothersRanjana MishraMeenakshi Bothra GuptaSharmila B MukherjeeAvinash LomashSangeeta GuptaSeema KapoorBackground: Biotin is the coenzyme of multiple carboxylases involved in gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Biotinidase (BTD) deficiency is an autosomal recessive disorder affecting the biotin cycle. It disrupts endogenous biotin recycling and results in multiple carboxylase deficiency depending upon the level of enzyme activity. Children with profound deficiency often present in infancy with neurocutaneous manifestations. Management of symptomatic children or screen-positive newborns is lifelong oral supplementation with biotin. There may be partial or complete resolution of symptoms in the former. Clinical Description: We describe two unrelated families diagnosed as profound BTD deficiency, with three affected children in each family. The first family had two symptomatic surviving children, a 2-year-old boy with seizures, developmental delay, and hearing loss, and a 1.5-month-old boy with seizures. Diagnosis was established while ascertaining etiology for seizures refractory to multiple anticonvulsant therapy. The second family was referred for postconceptional counseling following two infantile deaths with similar phenotype, early-onset seizures, encephalopathy, and acute metabolic decompensation. Management: The affected children in the first family showed a dramatic response in seizure controls with oral biotin though the other symptoms such as developmental delay and hearing loss remained unaffected. Mother was advised regarding prenatal diagnosis in the next pregnancy but was unwilling. In the second family, stored genetic material from the earlier affected infant revealed a pathogenic homozygous indel in the BTD gene, which was confirmed in utero in the subsequent pregnancy. Both women were started on oral biotin on the lines of antenatal management of holocarboxylase synthetase deficiency. After birth, therapy was continued on the confirmation of profound BTD deficiency in both babies. They have remained asymptomatic on follow-up; the first baby till a year and the second till 3 months. Conclusion: There is a considerable phenotypic variability in profound BTD deficiency. Early detection and prompt treatment with biotin may result in complete resolution of some symptoms and ameliorate others. Antenatal biotin supplementation in families at high risk or with prenatal diagnosis of BTD deficiency may have a favorable outcome in affected progeny.http://www.ipcares.org/article.asp?issn=2772-5170;year=2022;volume=2;issue=1;spage=12;epage=16;aulast=Mishraalopeciaencephalopathyhearing lossmultiple carboxylase deficiencyseizures |
| spellingShingle | Ranjana Mishra Meenakshi Bothra Gupta Sharmila B Mukherjee Avinash Lomash Sangeeta Gupta Seema Kapoor Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers Indian Pediatrics Case Reports alopecia encephalopathy hearing loss multiple carboxylase deficiency seizures |
| title | Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| title_full | Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| title_fullStr | Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| title_full_unstemmed | Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| title_short | Biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| title_sort | biotin supplementation in children with symptomatic profound biotinidase deficiency and their pregnant mothers |
| topic | alopecia encephalopathy hearing loss multiple carboxylase deficiency seizures |
| url | http://www.ipcares.org/article.asp?issn=2772-5170;year=2022;volume=2;issue=1;spage=12;epage=16;aulast=Mishra |
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