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Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported....

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Autores principales: Zhang, Weifeng, Chen, Yanru, Lin, Chunmei, Peng, Weilin, Fu, Qingliu, Lin, Yiming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633485/
https://www.ncbi.nlm.nih.gov/pubmed/34869124
http://dx.doi.org/10.3389/fped.2021.771922
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author Zhang, Weifeng
Chen, Yanru
Lin, Chunmei
Peng, Weilin
Fu, Qingliu
Lin, Yiming
author_facet Zhang, Weifeng
Chen, Yanru
Lin, Chunmei
Peng, Weilin
Fu, Qingliu
Lin, Yiming
author_sort Zhang, Weifeng
collection PubMed
description Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported. This study aimed to determine the biochemical, clinical, and genetic characteristics of patients with CPT1A deficiency in China. A total of 204,777 newborns were screened using tandem mass spectrometry at Quanzhou Maternity and Children's Hospital between January 2017 and December 2018. Newborns with elevated C0 levels were recruited, and suspected patients were subjected to further genetic analysis. Additionally, all Chinese patients genetically diagnosed with CPT1A deficiency were reviewed and included in the study. Among the 204,777 screened newborns, two patients were diagnosed with CPT1A deficiency; thus, the estimated incidence in the selected population was 1:102,388. In addition to the two patients newly diagnosed with CPT1A deficiency, we included in our cohort 10 Chinese patients who were previously diagnosed. Five of these 12 patients were diagnosed via NBS. All patients exhibited elevated C0 and/or C0/(C16+C18) ratios. No clinical symptoms were observed in the five patients diagnosed via NBS, while all seven patients presented with clinical symptoms, including fever, cough, vomiting, diarrhea, and seizures. Eighteen distinct CPT1A variants were identified, 15 of which have been previously reported. The three novel variants were c.272T>C (p.L91P), c.734G>A (p.R245Q), and c.1336G>A (p.G446S). in silico analysis suggested that all three novel variants were potentially pathogenic. The most common variant was c.2201T>C (p.F734S), with an allelic frequency of 16.67% (4/24). Our findings demonstrated that NBS for CPT1A deficiency is beneficial. The three novel variants expand the mutational spectrum of CPT1A in the Chinese population, and c.2201T>C (p.F734S) may be a potential hotspot CPT1A mutation.
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spelling pubmed-86334852021-12-02 Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency Zhang, Weifeng Chen, Yanru Lin, Chunmei Peng, Weilin Fu, Qingliu Lin, Yiming Front Pediatr Pediatrics Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported. This study aimed to determine the biochemical, clinical, and genetic characteristics of patients with CPT1A deficiency in China. A total of 204,777 newborns were screened using tandem mass spectrometry at Quanzhou Maternity and Children's Hospital between January 2017 and December 2018. Newborns with elevated C0 levels were recruited, and suspected patients were subjected to further genetic analysis. Additionally, all Chinese patients genetically diagnosed with CPT1A deficiency were reviewed and included in the study. Among the 204,777 screened newborns, two patients were diagnosed with CPT1A deficiency; thus, the estimated incidence in the selected population was 1:102,388. In addition to the two patients newly diagnosed with CPT1A deficiency, we included in our cohort 10 Chinese patients who were previously diagnosed. Five of these 12 patients were diagnosed via NBS. All patients exhibited elevated C0 and/or C0/(C16+C18) ratios. No clinical symptoms were observed in the five patients diagnosed via NBS, while all seven patients presented with clinical symptoms, including fever, cough, vomiting, diarrhea, and seizures. Eighteen distinct CPT1A variants were identified, 15 of which have been previously reported. The three novel variants were c.272T>C (p.L91P), c.734G>A (p.R245Q), and c.1336G>A (p.G446S). in silico analysis suggested that all three novel variants were potentially pathogenic. The most common variant was c.2201T>C (p.F734S), with an allelic frequency of 16.67% (4/24). Our findings demonstrated that NBS for CPT1A deficiency is beneficial. The three novel variants expand the mutational spectrum of CPT1A in the Chinese population, and c.2201T>C (p.F734S) may be a potential hotspot CPT1A mutation. Frontiers Media S.A. 2021-11-12 /pmc/articles/PMC8633485/ /pubmed/34869124 http://dx.doi.org/10.3389/fped.2021.771922 Text en Copyright © 2021 Zhang, Chen, Lin, Peng, Fu and Lin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Zhang, Weifeng
Chen, Yanru
Lin, Chunmei
Peng, Weilin
Fu, Qingliu
Lin, Yiming
Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title_full Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title_fullStr Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title_full_unstemmed Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title_short Three Novel and One Potential Hotspot CPT1A Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency
title_sort three novel and one potential hotspot cpt1a variants in chinese patients with carnitine palmitoyltransferase 1a deficiency
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633485/
https://www.ncbi.nlm.nih.gov/pubmed/34869124
http://dx.doi.org/10.3389/fped.2021.771922
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