Original articleClinical phenotype of mitochondrial diabetes due to rare mitochondrial DNA mutationsPhénotype clinique du diabète mitochondrial induit par des mutations rares de l’ADN mitochondrial
Section snippets
Abbreviations
- MIDD
Maternally Inherited Diabetes and Deafness
- MERFF
Myoclonic Epilepsy with Ragged Red Fibers
- mtDNA
mitochondrial DNA
- IU
International Unit
Study design
In order to determine the phenotype of rare mitochondrial mutations associated with diabetes, two groups were compared:
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the first one comprised rare mitochondrial mutations identified in 2 subgroups: the French Network of Mitochondrial Diseases, and a literature review on PubMed database;
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the second one (considered as control group) included patients with classical phenotype associated with the most frequent mtDNA mutation, m.3243 A>G, published by the GEDIAM (Mitochondrial Diabetes French Study
Patients with rare mitochondrial mutations from the French Network of mitochondrial diseases
In the princeps study [10], 45 of the 743 patients (6%) had diabetes. Ten carried a confirmed or putative pathogenic point mutation (22%). The characteristics of these ten patients are detailed in Table 1. The sex ratio was 1:1. Family history suggestive of mitochondrial disease in accordance with maternal transmission was present in 4 patients, absent in 5 and unspecified in 1. Further data about diabetes (natural history and glycemic control) were obtained for 6 of the 10 patients, as follows:
Discussion
Although the m.3243 A>G mtDNA mutation is the most frequent variant associated with mitochondrial diabetes, other point mutations can be responsible for clinical presentations involving diabetes. However, few data are available regarding their role in mitochondrial pathology. Through a review of the literature and a prospective clinical study, we identified 50 patients with diabetes due to rare mtDNA mutations and showed that these patients more frequently exhibited neurological symptoms, while
Conclusion
For clinicians, the main concern is probably to consider a diagnosis of mitochondrial diabetes. Clinical selection of patients is crucial in order to maximize molecular diagnosis of mitochondrial diabetes. Close collaboration with medical geneticists is essential to determine the most appropriate diagnostic strategy, given the major implications not only for the patient but also for the family, who get access to genetic counseling.
A diagnosis of mitochondrial diabetes must be considered in case
Disclosure of interest
The authors declare that they have no competing interest.
Ethics
Blood and tissue samples were taken after parents of affected children and adult patients had given informed consent. Authorizations for individual data protection were obtained through our Institutional Ethics Committee.
Funding
This work was made possible by grants to VP-F from the French Ministry of Health (PSTIC 2008, Programme de Soutien aux Techniques Innovantes et Coûteuses).
Contributions of the authors
Inclusion of patients by A.G.D.P., S.B., V.P., A.S.L., C.J., B.V., V.P.F., writing by A.G.D.P. and N.C., correction by N.C., V.P.F., S.B.
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