Pedigree Analysis Of Mitochondrial Diabetes

ObjectiveIn recent years, with the developing studies of the mitochondrial diseases，mitochondrial diabetes mellitus, as a specific type of diabetes that was frequently reportedin these years, was more and more recognised. Mitochondrial tRNALeu(UUR)3243A→Gmutation was the most common and acknowledged causative agent. The clinicalmanifestations of mitochondrial diabetes mellitus were various, but its early phenotypeswere much similar with type-1-diabetes and type-2-diabetes, so it was easy to get a wrongor a missed diagnosis and incorrect treatment, which would in turn accelerate thedevelopment of this disease. In this paper, we disscussed a case of diabetes mellitus causedby mitochondrial mutation of tRNALeu(UUR)3243A→G, mastered its clinical featuresand therapeutic principles, so to give a further recognition on the pathogenesis of thisdisease. As a result, we could improve the accuracy of the clinical diagnosis, reduce thecases misdiagnosed, the patients could be directly treated as early as possible, and all thefamily members would have a better quality of life.MethodsWe had collected a case of diabetes mellitus caused by mutation of mtRNALeu(UUR)3243A→G, and descibed the development of the disease, gene detection andpathology of muscle biopsy and the process of the treatment in detail. We also carried on ageneral research on14maternal members and detected the gene3243and other relatedgenes. At the same time, we referred to the domestic and overseas literature or reports onmitochondrial diabetes mellitus, combined the clinical resources and the literature,summed up the clinical phenotypes of mitochondrial diabetes mellitus, and analyzed itspathogenetic features. We also proved a reasonable therapeutic schedule for the family inthis paper.ResultsMuscle biopsy of the patient showed the pathologic features of mitochondrialencephalomyopathy. Both the patient (Ⅲ1)and her brother(Ⅲ3)were detected of the mtRNALeu(UUR)3243A→G mutation, while other maternal members were not.Meanwhile, we found three other mitochondrial variants in all the maternal members:A→G mutation in gene4769, A→G mutation in gene8860and the A→G mutation ingene15326. Mitochondrial diabetes mellitus was caused by mutations of DNA which ledto disorders of the mitochondrial oxidative phosphorylation, and then made a deficient ofenegy. The clinical manifestations of mitochondrial diabetes mellitus were various andheterogeneitied. The clinical features were concluded as follows: a thin somatotype, anearly onset(always younger than40years old), maternal inheritance, with nerve deafnessand always combined with other diseases such as MELAS, progressive retrogression ofbeta-cell’s function, while unobvious insulin resistance. To confirm the diagnosis, genedetection was always needed, muscle biopsy could also provide diagnostic evidences.Recently gene detection with RCR technics had widely been used in clinical application.The treatments of this disease were as follows: diabetic diet, avoiding aggravatingactivities and drugs of biguanides, and adding insulin as soon as possible. At the same time,coenzyme Q10and other symptomatic treatments were better choices to improvemetabolism.ConclusionAs a specific type of diabetes, mitochondrial diabetes mellitus had its specificity on itspathogenesis, clinical manifestations and treatments. Missed diagnosis or misdiagnosis inclinical work would easily result in a rapid and nonreversible progression. We shouldenhance the recognicion on mitochondrial diabetes mellitus, and make correct and earlydiagnosis. An early and correct diagnosis and effective therapies were better for directiontherapy for patients and estimating the risks for other members in their family. The exactdiagnosis relied on gene test. The mitochondrial mutation rates were various in differenttissues, thus it was necessary to take samples from the tissues with high mutation rates, soas to improve the detection rates. Except the mtRNALeu(UUR)A3243G mutation, someother variants might be also involved in the pathophysiological process of the disease. Andwe needed further studies on gene therapy other than general therapy to cure mitochondrialdiabetes mellitus radically.