Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA).
3243 A.G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with
a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic
children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing
impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in
three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the
mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was
3243A.G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We
measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers
than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was
lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown
association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered
a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in
children. The whole mtDNA should be screened because the 3243A.G variant is not as frequent in children as in adults. In
fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with
which to confirm the pathogenic significance of detected variants
