Carnitine-acylcarnitine translocase deficiency

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare, life-threatening inherited disorder of fatty acid oxidation caused by mutations in the SLC25A20 gene. The carnitine-acylcarnitine translocase enzyme is located in the inner mitochondrial membrane and is essential for transporting long-chain fatty acids into the mitochondria, where they are broken down to produce energy. When this enzyme is deficient, the body cannot properly use long-chain fatty acids as a fuel source, particularly during periods of fasting or physiological stress. The disease primarily affects the heart, liver, skeletal muscles, and brain. It most commonly presents in the neonatal period with severe symptoms including hypoketotic hypoglycemia (low blood sugar without appropriate ketone production), hyperammonemia (elevated blood ammonia), cardiomyopathy (weakened heart muscle), cardiac arrhythmias, seizures, hepatic dysfunction, skeletal muscle weakness, and respiratory distress. Episodes of metabolic crisis can be triggered by fasting, illness, or other metabolic stressors and can be fatal if not promptly treated. Elevated levels of long-chain acylcarnitines in the blood and decreased free carnitine are characteristic biochemical findings. Treatment focuses on preventing metabolic crises through avoidance of fasting, dietary management with restriction of long-chain fatty acids, and supplementation with medium-chain triglycerides (MCT) as an alternative energy source. Carnitine supplementation may also be considered, though its use remains debated. During acute metabolic crises, intravenous glucose is administered to suppress fatty acid oxidation. Despite treatment, the severe neonatal-onset form carries a high mortality rate. A milder phenotype with later onset and better prognosis has been described in some patients. Newborn screening programs using tandem mass spectrometry can identify affected infants before symptom onset, potentially improving outcomes through early intervention.

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