Four major forms of symptoms:
- Fatal infantile encephalomyopathy, congenital lactic acidosis, hypotonia, dystonic posturing, seizures, and coma. Ragged-red fibers are common. Some infants present a characteristic set of symptoms and signs: delayed growth, aminoaciduria, cholestasis (block of the liver bile ducts), iron overload, lactic acidosis, and early death (GRACILE syndrome).
- Encephalomyopathies of later onset (childhood to adult life): various combinations of weakness, short stature, ataxia, dementia, hearing loss, sensory neuropathy, pigmentary retinopathy, and pyramidal signs. Ragged-red fibers common. Possible lactic acidosis.
- Myopathy, with exercise intolerance and sometimes recurrent myoglobinuria. Ragged-red fibers are usually present: notably, they stain positively for the COX reaction. Possible lactic acidosis.
- Infantile histiocytoid cardiomyopathy.
Transmission is generally autosomal recessive, but mutations in the cytochrome b gene are transmitted maternally or are sporadic.