Deafness as a clue to the genetic transmission of diabetes: a case report, commentary, and recommendations

Czech version

Authors: Jozef Lacka ¹; Barbora Lacková ²
Authors‘ workplace: JAL, s. r. o., Trnava ¹; Interní oddělení, ambulance obezitologie, Nemocnice Rudolfa a Stefanie Benešov, a. s., Nemocnice Středočeského kraje ²
Published in: Diab Obez 2026; 26(1): 42-46
Category: Case studies

Overview

Maternally inherited diabetes and deafness (MIDD) is a rare form of monogenic diabetes caused by mutations in mitochondrial DNA, most commonly m.3243A>G, characterized by maternal inheritance and the combination of diabetes and sensorineural hearing loss. We present a case of a female patient whose diabetes was initially classified as type 2 diabetes mellitus following gestational diabetes. Recurrent spontaneous miscarriages, a family history of hearing impairment, and the occurrence of epilepsy in her offspring raised suspicion of a mitochondrial disorder. Molecular genetic testing confirmed the presence of the pathogenic m.3243A>G variant in a heteroplasmic state, establishing the diagnosis of MIDD. The case report highlights the importance of a thorough family history and the need for differential diagnostic consideration of monogenic forms of diabetes. From a therapeutic perspective, it is important to avoid medications that interfere with mitochondrial metabolism, particularly metformin due to the risk of lactic acidosis; treatment with sulfonylurea derivatives is also not appropriate. Suitable alternatives include therapy with GLP-1 receptor agonists or insulin. Early diagnosis of MIDD enables appropriate treatment selection, reduces the risk of complications, and allows targeted screening of maternal relatives.

Keywords:

sensorineural hearing loss – maternally inherited diabetes and deafness (MIDD) – mitochondrial diabetes

Sources

Murphy R, Turnbull DM, Walker M et al. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med 2008; 25(4): 383–399. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1464–5491.2008.02359.x>.
Maassen JA, ’t Hart LM, Van Essen E et al. Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 2004; 53(Suppl 1): S103–S109. Dostupné z DOI: <http://dx.doi.org/10.2337/diabetes.53.2007.s103>.
Suzuki S, Oka Y, Kadowaki T et al. Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (AG) mutation in Japanese. Diabetes Res Clin Pract 2003; 59(3): 207–213. Dostupné z DOI: <http://dx.doi.org/10.1016/s0168–8227(02)00246–2>.
Ali AS, Ekinci EI, Pyrlis F et al. Maternally inherited diabetes and deafness (MIDD): An uncommon but important cause of diabetes. Endocrine and Metabolic Science 2021; 2 : 100074.
Gorman GS, Chinnery PF, DiMauro S et al. Mitochondrial diseases. Nat Rev Dis Primers. 2016; 2 : 16080. Dostupné z DOI: <http://dx.doi.org/10.1038/nrdp.2016.80>.
Rho EH, Baek AI, Lee H et al. Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea. Diabetes Metab J 2024; 48(3): 482–486. Dostupné z DOI: <http://doi: 10.4093/dmj.2023.0078>.
Kyriakidou A, Hadjivassiliou M, Papapostolou A et al. Maternally Inherited Diabetes and Deafness (MIDD) –⁠ Atypical Clinical Diabetes Features Leading to the Diagnosis. JCEM Case Rep 2023;1(3): luad047. Dostupné z DOI: <http://doi: 10.1210/jcemcr/luad047>.
Chaudhry A, Thompson DM, Chanoine JP. Diabetes management in maternally inherited diabetes and deafness (MIDD): A review and a proposed treatment algorithm. Diab Obez Metab 2026; 28(2): 826–839. Dostupné z DOI: <https://doi.org/10.1111/dom.70240>.
Agrawal PK, Pursnani N, Gautam A et el. Maternally inherited diabetes and deafness: a case report and review of literature. J Diab Metab 2023; 14(3):173–176. Dostupné z DOI: <https://doi 10.4103/jod.jod_21_23>.
Wen H, Deng H, Li B et al. Mitochondrial diseases: from molecular mechanisms to therapeutic advances. Signal Transduct Target Ther 2025; 10 : 9. Dostupné z DOI: <https://doi.org/10.1038/s41392–024–02044–3>.
Chu KY et al. Mitochondrial DNA A3243G variant: Current perspectives and clinical implications. Intractable Rare Dis Res 2025; 14(4): 249–257.Dostupné z DOI: <http://doi 10.5582/irdr.2025.01051>.
El-Hattab AW, Adesina AM, Jones J et al. MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab 2015; 116(1–2):4–12. Dostupné z DOI: <http://doi 10.1016/j.ymgme.2015.06.004>.
Finsterer J. A Review of the Advances in the Medical Management of Epilepsy Associated With Myoclonic Epilepsy With Ragged-Red Fibers (MERRF) Syndrome. Cureus 2025; 17(4): e82875. Dostupné z DOI: <http://dx.doi.org/10.7759/cureus.82875>.
Aldossary AA, Tawfik EA, Alomary MN et al. Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives. Saudi Pharmaceutical J 2022; 30(8): 1065–1078. Dostupné z DOI: <https://doi.org/10.1016/j.jsps.2022.05.011>.
Zhang X et al. Mitochondrial disease and epilepsy in children. Front Neurol 2025;15 : 1499876. Dostupné z DOI: <https://doi 10.3389/fneur.2024.1499876.>.
Proks P, Reimann F, Green N et al Sulfonylurea stimulation of insulin secretion. Diabetes 2002; 51(Suppl 3): S368–S376. Dostupné z DOI: <http://dx.doi.org/10.2337/diabetes.51.2007.s368>.
Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia 2017; 60(5): 769–777. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–017–4226–2>.
Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target. Pharmacol Rev 2002; 54(1): 101–127. Dostupné z DOI: <http://dx.doi.org/10.1124/pr.54.1.101>.