As the acronym MELAS suggests, this disease is characterized by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms. At the first Child Neurological Society meeting, mitochondrial encephalomyopathy was introduced as “a group of neuromuscular disorders with defects in the oxidative pathways of energy production.” It presented with encephalomyopathy accompanied by many other symptoms.
The clinical constellation of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome was first characterized in a report on two patients with the clinical presentations described in the name. In other patients reported in the literature, ragged red muscle fibers suggested an abnormality of the electron transport system, but at this time, the precise biochemical disorders in these three clinical syndromes remained to be elucidated.
Although the clinical features are relatively distinctive, the biochemical abnormalities reported so far have not been uniform across cases, therefore implying a syndrome. Again, “ragged-red fibers were seen, but biochemical analysis showed increased subsarcolemmal activity in NADH tetrazolium reductase stain. Although this patient lacked muscle symptoms initially, she was diagnosed with MELAS on the basis of her CNS symptomatology; the authors hypothesize that mitochondrial changes in some MELAS patients may be due to chronic hypoxia.
The research indicates that when the mitochondria cause defects in OXPHOS,
increasing production of reactive oxygen species (ROS), this triggers the activation
of the cell death pathway. Autophagy inpatient-specific induced pluripotent
stem (iPS) from fibroblasts of patients with MELAS had well-characterized
mitochondrial DNA mutations and distinct OXPHOS defects. An increase in
autophagy was observed when compared with its normal counterpart, whereas
mitophagy is very scarce contributing to decreased cellular viability.