Delayed Biotin Therapy in a Child with Atypical Profound Biotinidase Deficiency: Late Arrival of the Truth and a Lesson Worth Thinking
-
Published:2023-06-16
Issue:12
Volume:24
Page:10239
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Liu Shu1ORCID, Zhang Ye1, Deng Zhi1, He Hui1, Zheng Xianhua2, Hong Qingshan3, Luo Xianqiong1
Affiliation:
1. Pediatric Endocrinology and Inherited Metabolic Department, Guangdong Women and Children Hospital, Guangzhou 511442, China 2. Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou 511442, China 3. Department of Radiology, Guangdong Women and Children Hospital, Guangzhou 511442, China
Abstract
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.
Funder
Natural Science Foundation of Guangdong Province Research Project of Traditional Chinese Medicine Bureau of Guangdong Province
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference26 articles.
1. Adam, M.P., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. (1993–2023). GeneReviews®, University of Washington. 24 March 2000 [updated 25 May 2023]. 2. Worldwide survey of neonatal screening for biotinidase deficiency;Wolf;J. Inherit. Metab. Dis.,1991 3. Sudden death associated with biotinidase deficiency;Burton;Pediatrics,1987 4. Why screen newborns for profound and partial biotinidase deficiency?;Wolf;Mol. Genet. Metab.,2015 5. Biotinidase deficiency: “If you have to have an inherited metabolic disease, this is the one to have”;Wolf;Genet. Med.,2012
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|