| Objective Maternally inherited diabetes and deafness(MIDD) is a special type of diabetes. In recent years, with the development and deep understood of mitoch ondrial diseases, clinical phenotype heterogeneity caused by mitochondrial 3243A>G mutation and the diversity of mitochondrial DNA mutation site in patients with diabetes were much higher than expected. This study investigate the clinical features and molecular genetic characteristics of mitochondrial diabetes through screening of clinically suspected patients with diabetes, to enhance the understanding of the pathogenesis of mitochondrial diabetes, to reduce the rate of misdiagnosis and missed diagnosis of MIDD and look for an early appropriate treatment.Methods The clinical data was collected from all the subjects. The genomic DNA was extracted from the peripheral blood, and the mt DNA3243 mutation was detected.Results Five probands were detected with mitochondrial 3243A>G mutation(prevalence was 6.25%). 9 cases of family members midd members with MIDD, they were early onset, the mean age of onset of diabetes was 31.2±7.2 years, low body weight, mean BMI was 18.85±1.48kg/m2, with varying degrees of neural deafness. Patients with short duration(≤ 5 years), the mean fasting C-peptide 1.28 + 0.56ng/m L, postprandial 2h C-peptide was 3.86±0.77ng/m L. longer duration(> 10 years) in patients with a mean fasting C-peptide 0.58±0.46ng/m L, postprandial 2h C-peptide was 1.44±0.55ng/m L, compared with T1 DM and T2 DM in C-peptide levels, P < 0.05, with an significant difference. 9 cases of MIDD patients with a poor blood glucose control, the average Hb A1 c was 10.1±3.0%, islet related antibody was negative, all members need for insulin therapy currentlly. In the course of the disease, 7 patients(7/8) showed the ventricular pre excitation or ST segment depression, 7 cases(7/8) in patients with bone loss or osteoporosis. 4 cases(4/6) with higher blood lactate. 5 cases(5/8) with diabetic peripheral neuropathy. All patients without cognitive disorders, epilepsy and other nervous symptoms. 3 cases(3 /5) family members were complicated with acute pancreatitis in the same time or after the diagnosis of diabetes in a pedigree with MIDD, and did not find a clear cause; 3 cases(3/8) carried the mt DNA3243A>G mutation with a normal glucose, the average age was 11.7 + 10.3 years, minimum age of only 10 years old, with poor growth, weight loss and other mitochondrial dysfunction, in which 2 cases showed a ST segment depression or ventricular pre-excitation syndrome. Another maternally inherited and deafness diabetes pedigree with a furniture late onset, chubby, elevation of blood lactic acid, hypertension, fatty liver, were not detected mutation in mt3243, but carried 11696G>A, and mutation rate is 1/100 in normal population in this locus, considered for the new mutation site of mitochondrial diabetes.Conclusion Mitochondrial diabetes is not rare, the clinical manifestations is diverse, maternal inherited, neural deafness as a feature, but the clinical may not be presented at the same time. Patients with early age, low weight, lactic acid, osteoporosis, poor postprandial insulin secretion should be suspected of mitochondrial diabetes. In addition to the classical mutation, the variant of 11696G>A may be related to the mitochondrial diabetes. The mt DNA mutation carrier need for multi-system tracking to get an early prevention, diagnosis and appropriate treatment. MIDD patients with decreased beta cell function, insulin therapy should be applied as early as possible, as well as the treament to improve mitochondrial function and reduce the antioxidant activity of reactive oxygen species. |
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