Clinical and genetic characteristics of young-onset diabetes with concurrent mitochondrial m.3243A>G and CEL gene mutations: A case report.

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.