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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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10239 |
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| author | Shu Liu Ye Zhang Zhi Deng Hui He Xianhua Zheng Qingshan Hong Xianqiong Luo |
| author_facet | Shu Liu Ye Zhang Zhi Deng Hui He Xianhua Zheng Qingshan Hong Xianqiong Luo |
| author_sort | Shu Liu |
| collection | DOAJ |
| 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 <i>BTD</i> 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 <i>BTD</i> 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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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:21:44Z |
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| spelling | doaj.art-ad622a68284844c190c20648e548d5b12023-11-18T10:50:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121023910.3390/ijms241210239Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth ThinkingShu Liu0Ye Zhang1Zhi Deng2Hui He3Xianhua Zheng4Qingshan Hong5Xianqiong Luo6Pediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaPediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaPediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaPediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaDepartment of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaDepartment of Radiology, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaPediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, ChinaBiotinidase (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 <i>BTD</i> 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 <i>BTD</i> 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.https://www.mdpi.com/1422-0067/24/12/10239biotinidase deficiency<i>BTD</i> genenovel variantorganic aciduriabiotin treatment |
| spellingShingle | Shu Liu Ye Zhang Zhi Deng Hui He Xianhua Zheng Qingshan Hong Xianqiong Luo Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking International Journal of Molecular Sciences biotinidase deficiency <i>BTD</i> gene novel variant organic aciduria biotin treatment |
| 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 | biotinidase deficiency <i>BTD</i> gene novel variant organic aciduria biotin treatment |
| url | https://www.mdpi.com/1422-0067/24/12/10239 |
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