Definition:

Myopathy with lactic acidosis and sideroblastic anaemia (MLASA) is a rare autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. MLASA has been associated with a missense mutation in pseudouridylate synthase 1 (PUS1), an enzyme located in both nucleus and mitochondria, which converts uridine into pseudouridine in several cytosolic and mitochondrial tRNA positions and increases the efficiency of protein synthesis in both compartments. Recently, it has been reported that a mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, also causes MLASA. Myopathy with succinate dehydrogenase and aconitase deficiency has been found to be caused by mutations in the gene encoding the iron-sulphur cluster scaffold protein (ISCU). ISCU is essential for the activity of mitochondrial iron-sulphur proteins such as succinate dehydrogenase and aconitase.