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Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report

BACKGROUND: Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been repor...

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Autores principales: Gan, Yi, Yu, Fei, Fang, Haining
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261918/
https://www.ncbi.nlm.nih.gov/pubmed/34233743
http://dx.doi.org/10.1186/s13052-021-01094-5
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author Gan, Yi
Yu, Fei
Fang, Haining
author_facet Gan, Yi
Yu, Fei
Fang, Haining
author_sort Gan, Yi
collection PubMed
description BACKGROUND: Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China. CASE PRESENTATION: A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16 + C18) ratio were detected by tandem mass spectrometry, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequence identified two mutations, c.2201 T > C (p.F734S) and c.1318G > A (p.A440T), in the patient. The c.2201 T > C mutation, which has been reported previously, was inherited from his father, while the c.1318G > A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic. CONCLUSION: This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. Three years follow-up suggested that early diagnosis and diet management may improve the prognosis in CPT1A patient. In addition, we identified a novel mutation c.1318G > A in CPT1A,and a possible unique to Chinese lineage mutation c.2201 T > C. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis.
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spelling pubmed-82619182021-07-07 Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report Gan, Yi Yu, Fei Fang, Haining Ital J Pediatr Case Report BACKGROUND: Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare mitochondrial fatty acid oxidation (FAO) disorder that results in hypoketotic hypoglycemia and hepatic encephalopathy. It is caused by mutation in CPT1A. To date, only two symptomatic cases of CPT1A deficiency have been reported in China. CASE PRESENTATION: A newborn male, without any disease-related clinical manifestations, was diagnosed with CPT1A deficiency through newborn screening. Increased free carnitine levels and a significantly increased C0/(C16 + C18) ratio were detected by tandem mass spectrometry, and subsequently, mutations in CPT1A were found by gene sequence analysis. The patient was advised a low-fat, high-protein diet and followed up regularly. During three-years of follow-up since, the patient showed normal growth velocity and developmental milestones. Whole-exome sequence identified two mutations, c.2201 T > C (p.F734S) and c.1318G > A (p.A440T), in the patient. The c.2201 T > C mutation, which has been reported previously, was inherited from his father, while the c.1318G > A, a novel mutation, was inherited from his mother. The amino acid residues encoded by original sequences are highly conserved across different species. These mutations slightly altered the three-dimensional structure of the protein, as analyzed by molecular modeling, suggesting that they may be pathogenic. CONCLUSION: This is the first case of CPT1A deficiency detected through newborn screening based on diagnostic levels of free carnitine, in China. Three years follow-up suggested that early diagnosis and diet management may improve the prognosis in CPT1A patient. In addition, we identified a novel mutation c.1318G > A in CPT1A,and a possible unique to Chinese lineage mutation c.2201 T > C. Our findings have expanded the gene spectrum of this rare condition and provided a basis for family genetic counseling and prenatal diagnosis. BioMed Central 2021-07-07 /pmc/articles/PMC8261918/ /pubmed/34233743 http://dx.doi.org/10.1186/s13052-021-01094-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Gan, Yi
Yu, Fei
Fang, Haining
Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title_full Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title_fullStr Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title_full_unstemmed Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title_short Novel mutation in carnitine palmitoyltransferase 1A detected through newborn screening for a presymptomatic case in China: a case report
title_sort novel mutation in carnitine palmitoyltransferase 1a detected through newborn screening for a presymptomatic case in china: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261918/
https://www.ncbi.nlm.nih.gov/pubmed/34233743
http://dx.doi.org/10.1186/s13052-021-01094-5
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