Clinical analysis of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes in children

Abstract

Objective To investigate the clinical, imaging, pathological and molecular biological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS) in children. Methods The clinical, imaging, pathological and molecular biological features of 12 children with MELAS diagnosed through muscle biopsy or gene sequencing in the Fifth Affiliated Hospital of Zhengzhou University from January 2011 to December 2015 were retrospectively analyzed. Results (1) Clinical features: the main manifestations included headache and vomiting in 11 cases, epileptic seizures in 9 cases, short stature in 8 cases, hairy in 7 cases, intolerance fatigue in 7 cases, cognitive decline in 7 cases, visual disturbance in 6 cases, hearing disturbance in 6 cases, and 5 cases had positive family history.In addition, 7 cases had the serum lactic acid level increase in a rest for 10 min after exercise.(2) Imaging features: 4 cases showed bilateral basal ganglia calcification symmetry in 8 patients who underwent head CT scan.The most frequently involved parts of the lesion were occipital in 10 cases, temporal in 9 cases and parietal lobe in 7 cases in stroke-like episodes.The lesions were lamellar necrosis.The abnormal areas by MRI showed low signal intensity on T1 weighted imaging, high signal intensity on T2 weighted imaging and fluid attenuated inversion recovery, high or equal signal intensity on diffusion weighted imaging, high or low signal intensity on apparent diffusion coefficient; the lactate peak significantly increased on magnetic resonance spectroscopy.The distribution was not in accordance with the control region of the cerebral vessels.Dynamic observation revealed that the lesions were reversible and migratory.(3) Myopathological features: muscle biopsy was performed in all children, and ragged-red fibers were found in 10 cases by improved Gomori staining, strongly succinate dehydrogenase-reactive were found in 9 cases, and the lipid droplets slightly increased in 8 cases by oil red O staining.Besides, the crystalline inclusion bodies in mitochondria were arranged in a parking lot pattern in 9 cases by electromicroscope.(4) Molecular biological characteristics: the mitochondrial gene mutations were analyzed in peripheral blood of 9 children and their parents, including 8 cases with A3243G mutation and 1 case with G13513A mutation.Five mothers had the same A3243G mutation site in 8 cases. Conclusions Children with MELAS have complex and varied clinical manifestations and certain characteristic of neuroimaging.Moreover, muscle pathology and gene sequencing have important diagnostic value.Fully understanding the clinical, muscle pathology, imaging and molecular biological characteristics of children with MELAS can be helpful to the early diagnosis and treatment, also reduce misdiagnosis. Key words: Mitochondrial encephalomyopathy; Lactic acidosis; Stroke-like episodes; Clinical manifestation