Endocrine Abstracts

Introduction: The mutation at m. 3243 adenine to guanine (A>G) in mitochondrial encoded transfer-RNA Leucine 1 (MTTL1) gene is the single most prevalent disease-causing mitochondrial DNA (MtDNA) mutation, with carrier status of 1:400 in our general population. The distinct disease phenotype is dependent on the level of heteroplasmy of wild-type vs mutation-type mtDNA in the specific target tissues, ranging from Maternally inherited diabetes and Deafness (MIDD) to mitochondrial encephalopathy lactic acidosis and stroke like episodes (MELAS). However, current studies have shown MELAS/MIDD overlap to be present (6%) but not without posing diagnostic dilemmas as current clinical criteria are based on classical features of one or the other with the likelihood of missing conditions with overlapping features.⁴

Case

A 33-year-old female with a background of MELAS and type 1 diabetes mellitus, admitted because of symptomatic uncontrolled capillary blood glucose levels and despite optimization of her insulin it was felt that she was unable to follow instructions. Further examination revealed sensorineural deafness and in light of previous genetic testing a diagnosis of MIDD was made. Her mother was also found to have m. 3243 A>G mutation with classical MIDD features.

Discussion: The case highlights the importance of recognizing patients with three of more clinical features of either MIDD or MELAS without the classical presentation and the need for genetic testing in these patients as well as in those with either classical MIDD or MELAS or overlap syndrome or with maternal history of m. 3243 A>G mutation.