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Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking

Biotinidase (BTD) deficiency (OMIM 253260) is an autosomal recessively inherited metabolic disorder resulting from deficient activity of the BTD enzyme, which can cleave and release biotin from a variety of biotin-dependent carboxylases, and is therefore recognized as a tool to recycle biotin. Being...

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Autores principales: Liu, Shu, Zhang, Ye, Deng, Zhi, He, Hui, Zheng, Xianhua, Hong, Qingshan, Luo, Xianqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299609/
https://www.ncbi.nlm.nih.gov/pubmed/37373384
http://dx.doi.org/10.3390/ijms241210239
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author Liu, Shu
Zhang, Ye
Deng, Zhi
He, Hui
Zheng, Xianhua
Hong, Qingshan
Luo, Xianqiong
author_facet Liu, Shu
Zhang, Ye
Deng, Zhi
He, Hui
Zheng, Xianhua
Hong, Qingshan
Luo, Xianqiong
author_sort Liu, Shu
collection PubMed
description Biotinidase (BTD) deficiency (OMIM 253260) is an autosomal recessively inherited metabolic disorder resulting from deficient activity of the BTD enzyme, which can cleave and release biotin from a variety of biotin-dependent carboxylases, and is therefore recognized as a tool to recycle biotin. Being a condition caused by variations on BTD gene with a consequence of free biotin shortage, BTD deficiency may impair the activity of biotin-dependent carboxylases, and thus bring about a buildup of potentially toxic compounds in the body, primarily 3-hydroxyisovaleryl-carnitine in plasma as well as 3-hydroxyisovaleric acid in urine. The phenotype of BTD deficiency may vary dramatically, from asymptomatic adults to severe neurological anomalies, even death in infancy. In the present study, we reported on a 5-month-old boy, whose parents sought for medical consultation in our clinic for their son due to his loss of consciousness, repeated tetany, and motor retardation. Detailed clinical features included severe psychomotor retardation, hypotonia, as well as failure to thrive. The brain MRI at 12 months showed cerebellar hypoplasia and multiple foci of leukodystrophy. The result of antiepileptic therapy was not satisfying. During hospitalization, BTD deficiency was suggested by elevated concentration of 3-hydroxyisovaleryl-carnitine in the blood spots and 3-hydroxyisovaleric acid in the urine. The child was then diagnosed with profound BTD deficiency based on the above findings and low BTD enzyme activity. Subsequent mutational analysis revealed a novel homozygous variant, c.637_637delC (p.H213Tfs*51) in exon 4 of BTD gene in the proband, which was recognized as a further support to the diagnosis. Therefore, biotin treatment was started immediately, eventually with satisfactory outcomes achieved in terms of prevention of epileptic seizure, performance in deep tendon reflexes, and improvement of muscular hypotonia, but unfortunately, the therapy failed to show any evident effects on poor feeding and intellectual disability. This painful lesson suggests that newborn screening for inherited metabolic diseases is essential for early identification and treatment, which should have been performed in this case to avoid this tragedy.
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spelling pubmed-102996092023-06-28 Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking Liu, Shu Zhang, Ye Deng, Zhi He, Hui Zheng, Xianhua Hong, Qingshan Luo, Xianqiong Int J Mol Sci Case Report Biotinidase (BTD) deficiency (OMIM 253260) is an autosomal recessively inherited metabolic disorder resulting from deficient activity of the BTD enzyme, which can cleave and release biotin from a variety of biotin-dependent carboxylases, and is therefore recognized as a tool to recycle biotin. Being a condition caused by variations on BTD gene with a consequence of free biotin shortage, BTD deficiency may impair the activity of biotin-dependent carboxylases, and thus bring about a buildup of potentially toxic compounds in the body, primarily 3-hydroxyisovaleryl-carnitine in plasma as well as 3-hydroxyisovaleric acid in urine. The phenotype of BTD deficiency may vary dramatically, from asymptomatic adults to severe neurological anomalies, even death in infancy. In the present study, we reported on a 5-month-old boy, whose parents sought for medical consultation in our clinic for their son due to his loss of consciousness, repeated tetany, and motor retardation. Detailed clinical features included severe psychomotor retardation, hypotonia, as well as failure to thrive. The brain MRI at 12 months showed cerebellar hypoplasia and multiple foci of leukodystrophy. The result of antiepileptic therapy was not satisfying. During hospitalization, BTD deficiency was suggested by elevated concentration of 3-hydroxyisovaleryl-carnitine in the blood spots and 3-hydroxyisovaleric acid in the urine. The child was then diagnosed with profound BTD deficiency based on the above findings and low BTD enzyme activity. Subsequent mutational analysis revealed a novel homozygous variant, c.637_637delC (p.H213Tfs*51) in exon 4 of BTD gene in the proband, which was recognized as a further support to the diagnosis. Therefore, biotin treatment was started immediately, eventually with satisfactory outcomes achieved in terms of prevention of epileptic seizure, performance in deep tendon reflexes, and improvement of muscular hypotonia, but unfortunately, the therapy failed to show any evident effects on poor feeding and intellectual disability. This painful lesson suggests that newborn screening for inherited metabolic diseases is essential for early identification and treatment, which should have been performed in this case to avoid this tragedy. MDPI 2023-06-16 /pmc/articles/PMC10299609/ /pubmed/37373384 http://dx.doi.org/10.3390/ijms241210239 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Liu, Shu
Zhang, Ye
Deng, Zhi
He, Hui
Zheng, Xianhua
Hong, Qingshan
Luo, Xianqiong
Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title_full Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title_fullStr Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title_full_unstemmed Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title_short Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
title_sort delayed biotin therapy in a child with atypical profound biotinidase deficiency: late arrival of the truth and a lesson worth thinking
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299609/
https://www.ncbi.nlm.nih.gov/pubmed/37373384
http://dx.doi.org/10.3390/ijms241210239
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