Clinical spectrum of the MELAS mutation in a large pedigree

Publisher Website
Google Scholar
Abstract
Introduction– MELAS is most often due to an maternally transmitted A-G transition mutation of mitochondrial DNA (nit DNA) at position 3243. In this study we report on the clinical spectrum associated with the mutation in the largest family reported so far. Patients and methods - In a family with three MELAS cases we identified 47 persons at risk for the mutation; sufficient data was available on 29. Mitochondrial disease was diagnosed in two of 9 deceased members (posthumous molecular analysis in one); 27 surviving family members underwent examination and 25 a molecular analysis of mt DNA from lymphoblasts. Then had a muscle biopsy and two were later autopsied. Results - All 26 cases investigated by molecular analysis showed the mutation at position 3243. The 18 symptomatic patients without stroke-like episodes had sensorineural hearing loss in 15 cases, diabetes in 6, nephropathy in 7, mild myopathy in 4, cardiomyopathy in 2, cerebellar disease in 4 and mental retardation in 2 cases. Eight carriers were asymptomatic. Autopsy showed > 80% mutant mt DNA in all tissues except blood (20%) examined in a MELAS patient, but Conclusions - The mutation of mt DNA at position 3243 causes a multisystem disorder with a variable phenotype due to heteroplasmy. Most carriers are oligosymptomatic with hearing loss and a variety of neurological and internal medical symptoms. Diabetes, cardiomyopathy and renal disease, which is newly reported here for this mutation, are frequent. The blood test is a reliable screening tool in affected families, but is of prognostic value only combined with examination of other tissues.