Endocrine Abstracts

Introduction: Maternally inherited diabetes and deafness (MIDD) that is caused by a pathogenic variant in mitochondrial DNA (mtDNA) can cause different phenotypes based on percent heteroplasmy load, with higher mutation load corresponding with disease severity. The m.A3243G mutation causes either classic MELAS or MIDD that is a partial form. The condition is characterised by diabetes, hearing impairment and maculopathy but can have several other clinical manifestations. Early recognition is important so that management of associated conditions and screening of maternal relatives can be implemented.

Case report: Caucasian female was incidentally diagnosed with type 2 diabetes aged 24 years during a routine medical check-up. BMI was 27 kg/m² at the time of diagnosis. She underwent some examinations: blood test included autoimmunity and genetic study for maturity-onset diabetes of the young (MODY) that were negative. C-peptide level: 2.87 ng/ml (1.1-4.4). Human leukocyte antigen (HLA) was positive for DR-4/DQ-8. Her diabetes was initially managed with lifestyle interventions, metformin and empagliflozin. Also has a medical history for hypertension, microalbuminuria, hypercholesterolaemia and bronchial asthma. She has hadn’t other complications. 4 years after diagnosis had sensorineural hearing loss so we request a genetic testing and found a probably pathogenic variant m.3243A>G heteroplasmy mutation in the MT-TL1 gene who is envolved in MIDD and MELAS syndrome. She has strong maternal family history of diabetes but no deafness. Following this diagnosis, she was referred for retinal screening where pigmented retinal lesions were found. The neurological evaluation was normal. Other hormones test were normal too. At the time of this diagnosis (6 yr after the beginning) she had a worsening of her blood glucose levels and Insulin was introduced into her medication regimen. We also changed empaglifozine for sitagliptin and added Co-enzyme Q10 (CoQ10).

Discussion: Recognizing mitochondrial disease in a cohort of patients with diabetes is not a simple task. It is not surprising, therefore, that it is common for mitochondrial diabetes to be misdiagnosed, even in the presence of other features that may provide clues as to the underlying genetic disease. Deafness usually precedes diabetes onset by 6 yr (intervals ranging 0-16) but in our patient deafness started 4 years after the diagnosis of diabetes. HLA polymorphisms associated with type1 diabetes as well as autoantibodies have only been anecdotally reported in mitochondrial diabetes mellitus (mDM). Reported cases were positive for HLA-DQA1/DQB1, but in our case, the polymorphism affected was DR4/DQ8 that isn’t described in the literature for mDM.