Mitochondrial diabetes and deafness: Possible dysfunction of strial marginal cells of the inner ear

Abstract

Objective: Some patients with the syndrome of mitochondrial diabetes and deafness (MIDD) have a m.3243A>G mutation of the MTTL1 gene encoding transfer ribonucleic acid for the amino acid leucine (tRNALeu(UUR)). One of our MIDD patients inspired us to propose an integrated view on how a single mutation of the mitochondrial deoxyribonucleic acid (DNA) affects both the glucose metabolism and the inner ear physiology. Design: (a) Study of mitochondrial DNA in a patient with MIDD. (b) Review of the literature on the impact of the m.3243A.G mutation on glucose metabolism and on the physiology of the hearing process. Settings: Outpatient diabetes and nutrition department and molecular nutrition laboratory. Methods: (a) Polymerase chain reaction followed by restriction fragment analysis identified the m.3243A>G mutation. (b) Review of the literature from 1994 to 2009. Results: (a) Molecular study: the m.3243A>G mutation was detected with an appreciable level of heteroplasmy. (b) Review of the literature: the strial marginal cells located near the organ of Corti fulfill two characteristics: they are rich in mitochondria, and their dysfunction may produce neurosensorial deafness by means of a reduction in the potassium ion concentration of the endolymph. Conclusions: The m.3243A>G mutation not only underlies a dysfunction of the insulin-producing beta cell of the pancreas but also results in a reduction in adenosine triphosphate production of the strial marginal cells of the inner ear, thus diminishing the energy (in the form of potassium ion gradient) needed for the outer hair cells of the organ of Corti to amplify the soundwaves, particularly at high frequencies. © 2011 The Canadian Society of Otolaryngology-Head & Neck Surgery.