Involvement of nervous system in maternally inherited diabetes and deafness (MIDD) with the A3243G mutation of mitochondrial DNA

Objectives - The A3243G mutation of mitochondrial DNA (mtDNA) has been asso ciated with maternally inherited diabetes and deafness (MIDD) in a number o f reports; however, the involvement of the nervous system has rarely been m entioned, prompting this exploration of the manifestation of neurological d isorders in MIDD cases. Material and methods - We investigated four generat ions of a large Taiwanese family in which MIDD is manifest. We conducted a series of clinical examinations, including computed tomography (CT) and mag netic resonance imaging (MRI) of the head, brain Tc-99m-HMPAO single photon emission computed tomography (SPECT), cognitive function tests, and nerve conduction velocity (NCV) studies. Blood levels of creatine kinase (CK) and lactate, pathology of muscle biopsy samples and proportions of mutant mtDN A in blood cells, hair follicles, muscle and skin were also analyzed. Mean followup period was 4 years. Results - The patients exhibited the clinical features of diabetes mellitus including sensorineural hearing loss, short s tature, and/or histories of spontaneous abortion. No stroke-like episodes w ere reported. Analysis for mtDNA revealed that the A3243G mutation existed in 11 members (6 symptomatic and 5 asymptomatic members) of this MIDD-prone family, with the proportion of mutant mtDNA ranging from 21% to 47% in leu kocytes. Head CT revealed diffuse brain atrophy for all 6 (100%) patients e xamined and bilateral basal ganglia calcification in 4 of 6 (67%) patients. Brain Tc-99m-HMPAO SPECT revealed diminished uptake in the bilateral parie to-occipital or occipital regions for all 6 tested patients, cognitive func tion for these patients was normal. Results of head CT and SPECT were norma l in one asymptomatic member of the family. One muscle biopsy revealed abun dant ragged-red fibers with modified Gomori-trichrome stain. Muscle-enzyme activity and serum-lactate levels were normal. Conclusion - We have demonst rated that a wide spectrum of sub clinical pathologies of the central nervo us system and muscle are present for this MIDD-prone family, none of whom d eveloped typical MELAS during the 4-year period of follow-up study.