Mitochondrial diabetes in relation to 40 patients from 30 tunisian families: phenotypic and genotypic heterogeneity

Hamdi Frikha; Yesmine Elloumi; Souhir Maalej; Khouloud Boujelben; Salah Dhoha Ben; Kacem Akid Faten Haj; Fatma Mnif; Nadia Charfi; Mouna Mnif; Mouna Elleuch; Mohamed Abid; Majdoub Nabila Rekik

doi:10.1530/endoabs.99.EP72

EP72

Prev Next

Section Contents Cite

Endocrine Abstracts (2024) 99 EP72 | DOI: 10.1530/endoabs.99.EP72

ECE2024 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (383 abstracts)

Mitochondrial diabetes in relation to 40 patients from 30 tunisian families: phenotypic and genotypic heterogeneity

Hamdi Frikha , Yesmine Elloumi , Souhir Maalej , Khouloud Boujelben , Dhoha Ben Salah , Faten Haj Kacem Akid , Fatma Mnif , Nadia Charfi , Mouna Mnif , Mouna Elleuch , Mohamed Abid & Nabila Rekik Majdoub

Views

Author affiliations

Hedi Chaker University Hospital, Department of Endocrinology, Tunisia

Introduction: Mitochondrial diabetes (MD) is characterized by a wide spectrum of phenotypic and genotypic manifestations. Through a cohort study of 40 patients with MD, we attempted to establish a correlation between this diversity of phenotypic expression and the biomolecular substrate of the mitochondrial genome within the Tunisian population.

Results: Epidemiologically and anthropometrically, our series aligns with literature data, with an onset age of 31.6 years (5-52), a female predominance (82.5%), and a normal BMI in 60% of cases. Diabetes had a MIDD2 phenotype in % of cases, with a significantly higher frequency of diabetic retinopathy (42.5%) compared to 8-13% in the literature. Regarding extra-pancreatic manifestations, the reticulated macular dystrophy, highly characteristic of MD, was absent in all our patients, as well as retinitis pigmentosa (15% vs 57-86%). Perceptive deafness, classically almost constant, was present in only half of the cases. Dilated cardiomyopathy was found in only one case vs 18-34% in the literature. The biomolecular study of the mitochondrial genome revealed the absence of the most frequently described mutation associated with MD: m.3243A>G (tRNA Leu). This led us to investigate the m.14709T>C (tRNA Glu) mutation, found in 6 patients from 3 different families; however, the study of heteroplasmy levels within 2 families did not reveal a correlation with the phenotypic spectrum. Moreover, whole mitochondrial genome sequencing revealed other polymorphisms not described in the literature, playing a key role in the functioning of the mitochondrial respiratory chain.

Conclusion: Our cohort is characterized by phenotypic and genotypic heterogeneity within a sample of the Tunisian population. It appears that the m.3243A>G mutation is not specific to our Tunisian population, and the m.14709T>C mutation was more frequent. A larger-scale study is necessary to establish the impact of heteroplasmy levels on the phenotypic spectrum.