Clinical features of the late ⁃ onset mitochondrial encephalomyopathy with lactic acidosis and stroke⁃like episodes

Abstract

Objective To summarize the clinical, pathological and genetic features of 10 patients with late ⁃ onset mitochondrial encephalomyopathy with lactic acidosis and stroke ⁃ like episodes (MELAS). Methods and Results The clinical data of 10 patients with late ⁃ onset MELAS were retrospectively analyzed from January 2007 to December 2018. Muscle biopsy was performed in 8 cases. Polymerase chain reaction ⁃ fragment length polymorphism (PCR⁃RFLP) analysis and whole sequencing of mitochondrial DNA (mtDNA) were used to screen mtDNA mutations, and the mutation load of m.3243A > G in blood was detected by pyrophosphate sequencing. The onset age of the first stroke ⁃like episodes were 40-67 years old in all patients. The main manifestations included epilepsy, aphasia, headache, dementia, mental disorder, limb paralysis and visual impairment. Past history revealed 5 cases with diabetes mellitus, 6 with deafness, 3 with hypertension and 2 with stroke. Six patients had a family history of maternally inherited diabetic mellitus, and 2 had a family history of MELAS. Laboratory examination revealed 6 cases with hyperlipidemia, 6 with carotid atherosclerosis, 1 with stenosis of right internal carotid artery and middle cerebral artery. Brain MRI showed cortex lesions involving one or more lobes in all patients, and 4 cases also had multiple infarctions in brainstem and basal ganglia. Muscle biopsy demonstrated ragged red fiber (RRF) and strongly succinate dehydrogenase ⁃ stained vessels (SSVs) in all of 8 patients except one. Genetic analysis identified 9 cases with m.3243A > G, and 1 with m.10191T > C mutation. The blood mutation load of m.3243A > G was 9%-33% in 7 cases. Conclusions The clinical phenotype of patients with late ⁃ onset MELAS was not significantly different from that of typical patients. However, the age of onset in late ⁃ onset MELAS was late, and it could be complicated with a variety of cerebrovascular risk factors and atherosclerosis. The hotspot mutation of this group of late ⁃ onset MELAS patients was m.3243A > G, but the mutation rate in blood was low.DOI：10.3969/j.issn.1672⁃6731.2020.03.015