FAODs

Fatty acid oxidation disorders (FAODs) are a group of inherited metabolic diseases caused by defects in the mitochondrial beta-oxidation pathway that normally converts long‑chain fatty acids into usable energy. These disorders can affect the liver, heart, and muscles and often present during infancy or adolescence, especially after fasting, illness, or strenuous exercise.

Most FAODs are inherited in an autosomal recessive pattern. The disorders are caused by defects in enzymes or transport proteins needed to remove long-chain fatty acids from the mitochondria or to break them down. Common examples include MCAD deficiency, VLCAD deficiency, LCHAD/CCHAD, CPT1A deficiency, CPT2 deficiency, and translocase defects. The clinical presentation varies by disorder and can range from asymptomatic to severe metabolic crises with hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and muscle weakness.

Diagnosis typically begins with a newborn screening program that uses an acylcarnitine profile. During a metabolic crisis, laboratory testing may show hypoketotic hypoglycemia, characteristic acylcarnitine patterns, and abnormal urinary organic acids. Genetic testing confirms the specific gene mutations (for example ACADM, ACADVL, CPT1A, CPT2, HADHA/HADHB). Early diagnosis is increasingly common due to newborn screening.

Management emphasizes prevention of decompensation: regular, frequent feeding to avoid fasting; a diet adapted to the disorder, often with reduced long-chain fat intake and, in some conditions, the use of medium-chain triglycerides; avoidance of prolonged fasting; and an emergency treatment plan for illness with prompt intravenous glucose. Some patients may receive carnitine supplementation depending on the specific disorder. Prognosis varies by type and timeliness of diagnosis and treatment, but newborn screening and proper management have markedly improved outcomes.