Symptoms of CcO deficiency manifest after the age of 2 years and in mild cases at adolescence and include hypertrophic cardiomyopathy, myopathy, hypotonia, encephalomyopathy, Leigh syndrome and lactic acidosis, which can cause nausea and irregular heartbeats and can be life threatening [133]. Here, RYR1 is linked to hyperinsulinemic hypoglycemia, familial, 4.