MIDD is a mitochondrial disorder characterized by diabetes and sensorineural deafness. Patients initially lose perception of higher frequencies, eventually progressing to complete hearing loss. Some individuals may also exhibit ocular anomalies such as macular pattern dystrophy and pigmentary retinal degeneration although this does not result in loss of visual acuity. Other variable symptoms include ptosis, cardiomyopathy, myopathy, renal problems and neuropsychiatric symptoms. MIDD is a rare condition and is seen in about 1% of diabetes cases. The onset of diabetes and deafness usually occurs in mid-adulthood. Compared to MELAS and other mitochondrial diseases with diabetes, MIDD has a better prognosis. While the disorder has been reported in several regions, it is found to be most common in the Japanese population.
The condition is diagnosed based on clinical features, the presence of deafness and evidence of maternal transmission. There is currently no cure for MIDD. Treatment is supportive and focused on oral antidiabetic agents or insulin therapy. Patients may also benefit from hearing aids or cochlear implants. Coenzyme Q10 supplementation is currently being researched as a possible treatment option.
MIDD is a maternally inherited disorder that can be caused by mutations in several mitochondrial genes, namely: MTTL1, MTTE and MTTK. The most common mutation associated with MIDD is the m.3243A>G transition seen in the MTTL1 gene. This gene encodes tRNA-Leu (UUR) which is responsible for the transfer of the amino acid leucine to its correct position during mitochondrial protein translation. The gene is also required for transcription termination of the mitochondrial genome.
Tabebi et al. (2016) described a multiplex consanguineous Tunisian family affected by MIDD and aimed to ascertain the underlying genetic defect. The authors studied three patients: a mother, along with her son and daughter. All three patients suffered from mitochondrial diabetes, deafness and obesity. In addition, the son also suffered from diabetic retinopathy. A whole mitochondrial genome mutational analysis helped reveal a haplotype composed by “A750G, A1438G, G8860A, T12705, T14766C and T16519C”, in homoplasmic state in all 3 patients. The family was classified under the sub-haplogroup H2a2a1. The son also had two de-novo variations: a novel m.8241T>G (p. F219C) in the MT-CO2 gene and the known m.13276G>A (p. M314V) in the MT-ND5 gene. The son’s severe phenotype was suggested to be due to the coexistence of these two mutations.
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