The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients

Mengge Yang, Lusi Xu, Chunmei Xu, Yuying Cui, Shan Jiang, Jianjun Dong, Lin Liao, Mengge Yang, Lusi Xu, Chunmei Xu, Yuying Cui, Shan Jiang, Jianjun Dong, Lin Liao

Abstract

Aims: To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.

Methods: PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "Maternally inherited diabetes and deafness" OR "MIDD" OR "Mitochondrial diabetes". The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.

Results: Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.

Conclusions: The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.

Keywords: diagnosis; heteroplasmy; maternally inherited diabetes and deafness; mitochondrial gene mutations; treatment.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Yang, Xu, Xu, Cui, Jiang, Dong and Liao.

Figures

Figure 1
Figure 1
(A) Geographical country distribution ratio among the patients (%), (B) the percentage of different mutation sites (%).
Figure 2
Figure 2
Clinical characteristics of patients with mitochondrial mutations. (A–D) The proportion of several clinical characteristics in enrolled patients: (A) gender (N: 161), (B) family histories (N: 142), (C) treatment (N: 102), and (D) BMI (N: 101).
Figure 3
Figure 3
Whisker plot for continuous clinical data of patients with mitochondrial mutations. (A–D) Continuous data for the variables of (A) Age at onset, (B) BMI, (C) Fasting C peptide, and (D) Period until insulin dependency.
Figure 4
Figure 4
Correlation between blood heteroplasmy levels and age at the onset of diabetes.

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