IARS1 and hyperinsulinemic hypoglycemia, familial, 4: Furthermore, we found a pathogenic variant in the cytoplasmic located aminoacyl-tRNA synthetase IARS to cause complex I deficiency in skin and muscle tissue of a patient with a multi-system disorder, and a defect in the acetylcholine receptor subunit epsilon CHRNE associated with CII deficiency, COX negative muscle fibers and abnormally shaped muscle mitochondria in CPEO with myopathy.