ACAD9 deficiency is a rare autosomal recessive mitochondrial disease. It is caused by a mutation in the ACAD9 gene (chromosome 3q21.3), which encodes a protein that helps assemble complex I in the electron transport chain. This protein also catalyzes the rate-limiting step in the beta-oxidation of 14- to 20-carbon chain length fatty acids. Fewer than 100 cases have been reported in the primary literature since the first case report was published in 2007. At least 16 pathogenic mutations in the ACAD9 gene have been identified. The exact location of the variants within the gene contributes to disease severity and age of onset.

ACAD9 is expressed throughout the body but especially in the brain, heart, liver, and skeletal muscles; thus, these organs are the most affected by ACAD9 deficiency. The clinical manifestations vary in severity, with neonates and infants presenting with life-threatening symptoms, whereas older children and adults manifest with milder cases. Adults with previously undiagnosed ACAD9 deficiency may present with growth retardation, learning difficulties, exercise intolerance, and fatigability.

The prevalence and demographic risk factors of ACAD9 deficiency are currently unknown because of the rarity and relatively recent discovery of this disorder.