Che XD, Wei ZL, Gong W, Qin L, Liu S, Jin YH, Wang HY. Clinical and genetic characteristics of young-onset diabetes with concurrent mitochondrial m.3243A>G and CEL gene mutations: A case report. World J Diabetes 2025; 16(12): 113238 [DOI: 10.4239/wjd.v16.i12.113238]
Corresponding Author of This Article
He-Yuan Wang, MD, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130000, Jilin Province, China. wangheyuan@jlu.edu.cn
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Endocrinology & Metabolism
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Case Report
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 15, 2025 (publication date) through Dec 15, 2025
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World Journal of Diabetes
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1948-9358
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Che XD, Wei ZL, Gong W, Qin L, Liu S, Jin YH, Wang HY. Clinical and genetic characteristics of young-onset diabetes with concurrent mitochondrial m.3243A>G and CEL gene mutations: A case report. World J Diabetes 2025; 16(12): 113238 [DOI: 10.4239/wjd.v16.i12.113238]
World J Diabetes. Dec 15, 2025; 16(12): 113238 Published online Dec 15, 2025. doi: 10.4239/wjd.v16.i12.113238
Clinical and genetic characteristics of young-onset diabetes with concurrent mitochondrial m.3243A>G and CEL gene mutations: A case report
Xiao-Dan Che, Zheng-Liang Wei, Wuriliga Gong, Ling Qin, Shuang Liu, Yuan-Hui Jin, He-Yuan Wang
Xiao-Dan Che, Ling Qin, Shuang Liu, Yuan-Hui Jin, Department of Endocrinology, Meihekou Central Hospital, Meihekou 135000, Jilin Province, China
Zheng-Liang Wei, Wuriliga Gong, He-Yuan Wang, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
Co-first authors: Xiao-Dan Che and Zheng-Liang Wei.
Co-corresponding authors: Yuan-Hui Jin and He-Yuan Wang.
Author contributions: Che XD and Wei ZL contribute equally to this study as co-first authors; Jin YH and Wang HY contribute equally to this study as co-corresponding authors; Che XD was responsible for investigation, writing-original draft; Wei ZL was responsible for visualization, writing original draft, conceptualization, investigation, supervision, writing-review & editing; Gong W was responsible for supervision, writing–review & editing; Qin L was responsible for investigation, writing-original draft; Liu S was responsible for supervision, writing-review & editing; Wang HY was responsible for writing-review & editing, supervision; Jin YH was responsible for writing–review & editing.
Supported by Jilin Province Science and Technology Development Project, No. 20220203018SF.
Informed consent statement: Written informed consent was obtained from the patient for publication of this report.
Conflict-of-interest statement: The authors declare no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: He-Yuan Wang, MD, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun 130000, Jilin Province, China. wangheyuan@jlu.edu.cn
Received: August 21, 2025 Revised: October 10, 2025 Accepted: November 18, 2025 Published online: December 15, 2025 Processing time: 116 Days and 16.7 Hours
Abstract
BACKGROUND
Only a few cases of diabetes mellitus with concurrent mutations in the mitochondrial MT-TL1 and CEL genes have been reported worldwide. Racial differences may influence mutation frequency, the presentation of symptoms, and disease progression. This case report describes the clinical features, potential genetic mechanisms, and diagnostic complexity of young-onset diabetes mellitus with concurrent m.3243A>G mutation in MT-TL1 and c.1336G>A mutation in CEL. The objective is to inform precise typing, genetic counseling, and personalized treatment of monogenic diabetes mellitus, while expanding the evidence base on rare forms of diabetes mellitus.
CASE SUMMARY
A 30-year-old man, diagnosed with diabetic ketoacidosis six years earlier, presented with poor response to insulin therapy (glycated hemoglobin, 15.35%), marked wasting (body mass index: 15.06 kg/m2), sensorineural deafness, diabetic retinopathy, and peripheral neuropathy. Whole-exome sequencing revealed concurrent mutations: Mitochondrial MT-TL1 m.3243A>G (heteroplasmy 41.76%) and CEL c.1336G>A. Family investigation identified his mother, who also had diabetes, as a carrier of the CEL mutation, and his sister as harboring both mutations without diabetes.
CONCLUSION
This case highlights the genetic heterogeneity of monogenic diabetes and expands the known mutational spectrum. Comprehensive genetic testing is recommended to enhance diagnostic accuracy in cases of suspected monogenic diabetes.
Core Tip: This case report describes a young man with diabetes mellitus attributable to concurrent mutations in the mitochondrial MT-TL1 gene (m.3243A>G) and the CEL gene (c.1336G>A). The patient exhibited atypical features, including diabetic ketoacidosis, severe weight loss, retinopathy, and hearing loss. Whole-exome sequencing identified both mutations, each linked to distinct diabetes subtypes. The study proposes a "two-hit" mechanism in which the mitochondrial mutation compromises β-cell function, whereas the CEL mutation exacerbates insulin deficiency. These findings highlight the importance of genetic testing in diagnosing rare forms of diabetes and tailoring treatment.
