Succinic acidemia

Succinic acidemia, also known as succinyl-CoA ligase deficiency or succinate-CoA ligase deficiency, is an extremely rare inherited metabolic disorder affecting mitochondrial energy metabolism. The condition is caused by deficiency of succinyl-CoA ligase (also called succinyl-CoA synthetase), an enzyme involved in the citric acid cycle (Krebs cycle), which is essential for cellular energy production. Mutations in the SUCLA2 or SUCLG1 genes have been identified as causative. The disorder primarily affects the nervous system and muscles, leading to mitochondrial DNA depletion syndrome. Clinical features typically present in infancy and include progressive encephalomyopathy, severe muscular hypotonia, psychomotor retardation, failure to thrive, and sensorineural hearing loss. Patients often exhibit elevated levels of succinic acid and methylmalonic acid in urine and blood. Lactic acidosis is a common metabolic finding. SUCLG1 mutations tend to cause a more severe phenotype with multisystem involvement including hepatic dysfunction, while SUCLA2 mutations are more commonly associated with a predominantly neurological and muscular phenotype. There is currently no curative treatment for succinic acidemia. Management is supportive and symptomatic, focusing on nutritional support, physical therapy, management of seizures if present, and monitoring for complications such as respiratory insufficiency. The prognosis is generally poor, particularly in severe forms, with many affected children experiencing progressive neurological decline. Early diagnosis through metabolic screening and genetic testing is important for family counseling and supportive care planning.

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