Endocrine Abstracts

Introduction/Aim: MIDD (maternally inherited diabetes and deafness) and MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) are rare, maternally inherited, multisystem disorders caused by mitochondrial DNA mutations. We present the case of a patient with mitochondrial diabetes and discuss the diagnostic challenges.

Case presentation: A 25-year-old female patient with a 7-year history of diabetes mellitus (DM) and suboptimal glycemic control (HbA1c 7.8%) on intensive insulin therapy was evaluated in our department. She reported no history of diabetic ketoacidosis, the total insulin dose was 1.21 IU/kg/day, serum C-peptide was 1.6 ng/ml and the antibodies associated with type 1 DM were negative. Family history: one sister diagnosed with MELAS syndrome (encephalopathy, epilepsy) and mother with insulin-treated DM since the age of 24 years and deafness. Clinical examination: Height 1.55m, BMI 28 kg/m², bilateral sensorineural deafness, retinal lesions. Cardiac ultrasound: mild left ventricular heart hypertrophy. On the basis of the medical history and clinical features a diagnosis of probable mitochondrial diabetes was made. Genetic analysis in both the patient and her mother revealed heteroplasmy for the pathogenic variant m.3243A> G in tRNA^{Leu (UUR)}, MT-TL1 gene.

Conclusions/Discussion: Various syndromes including MIDD, MELAS and CPEO (chronic progressive external ophthalmoplegia) are caused by the mutation m.3243A> G. Although there is a significant phenotypic overlap, DM is a common feature of all three syndromes. In these rare, maternally inherited, mitochondrial disorders, multiple systems are affected (neuromuscular, eyes, heart, pancreas), and diabetes is due to a combination of insulin secretory defect as well as insulin resistance. It is estimated that mitochondrial DM is the cause of ~1% of the total DM population and m.3234A> G is the responsible pathogenic variant in over 85% of these cases. The therapeutic choices include insulin, incretin analogs and/or oral antidiabetic medications. Metformin is however avoided because of the risk of lactic acidosis. Although there is no curative treatment, correct diagnosis of mitochondrial diabetes is necessary for the optimal management and genetic counselling of these patients.