Shasha Zheng

and 7 more

IntroductionMitochondrial disease (MD) is a group of disorders caused by dysfunctional mitochondria, the organelles which play an important role in the production of ATP and exist in every human cell inthe body, except for the red blood cells (1 ). Mitochondrial DNA (mtDNA) is inherited maternally and affects organs dependent on high aerobic metabolism, such as the eye, inner ear, central nervous system, skeletal and cardiac muscle. Mitochondrial diabetes mellitus (MDM), also known internationally as maternally inherited diabetes and deafness (MIDD) syndrome, is a mtDNA mutation disease, with a progressive islet β cell secretory dysfunction (2, 3 ). MIDD is associated with early onset diabetes and sensorineural deafness, but there are various other systemic features, including cardiomyopathy, renal problems, and neuropsychiatric symptoms. It was first reported by J.A. Massen et al. in 1992, who found a large pedigree with mt.3243A>G mutation, suffering from diabetes with the presence of maternal transmission, in conjunction with bilateral hearing loss in most of the carriers (4 ). From then on, there has been growing scientific evidence that a range of other point mutations in mtDNA could contribute to the pathogenesis of MIDD, such as mt-tRNA encoding genes, including MT-TI, MT-TS1, and MT-TK, and mt-proteins encoding genes, incuding MT-ND1, MT-ND4, MT-COX2, and MT-COX3. In addition, deletion and depletion of nucleotides have also been described in patients with MIDD (5 ). These novel mutations, however, are extremely rare compared to the proportion of mt.3243A>G, where there is an A to G substitution at position 3243. MIDD is currently found to be the most common type of monogenic diabetes mellitus, accounting for about 1% of all diabetes mellitus, and the incidence in China is approximately 0.6% (6 ). Because of its low incidence and irrespective of its complex clinical phenotype, MIDD is often misdiagnosed as type 1 or type 2 diabetes. Nonetheless, its treatment is different from the common types of diabetes, and incorrect diagnosis and treatment will accelerate the disease process and the occurrence of complications. Therefore, correct genetic diagnosis and treatment are crucial for patients with MIDD. This study discusses the clinical manifestations and treatment process of a typical patient with MIDD, and summarizes its clinical characteristics through a comprehensive review of the literature, with the scope of improving clinicians’ cognition of the disease and reducing misdiagnosis rate.