Infants feed poorly which is frequently associated with vomiting, failure to thrive, and growth delay. They are hypothermic, hypoglycemic, and often jaundiced with signs of liver failure noted between birth and 6 months of age and death by approximately 1 year of age. Hepatosplenomegaly is present early with abnormal liver enzymes, cholestasis, steatosis, and hepatocellular loss followed by cirrhosis with portal hypertension. Metabolic acidosis, hyperbilirubinemia, hypoalbuminemia, and hypoglycemia are often present. Mitochondrial DNA depletion in the liver approaches 84-90%.
All patients have encephalopathic signs with evidence of cerebral atrophy, microcephaly, hypotonia. Hyperreflexia may be present and some infants have seizures. Muscle tissue, however, has normal histology and respiratory chain activity.