Aug. 25, 2023
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Carnitine-acylcarnitine translocase deficiency is a rare inborn error of energy metabolism involving the carnitine cycle and long-chain fatty acid oxidation. This enzyme deficiency is considered the most severe disorder of fatty acid oxidation. Its clinical features are related to the impairment of fasting adaptation and cardiac and skeletal muscle metabolism, and its presentation overlaps with the clinical presentation of the severe neonatal form of carnitine palmitoyltransferase type-2 deficiency. In this article, the author describes the developments of this disorder, including the expanding clinical phenotype, management, and advances in the understanding of the genetics of this condition since the human gene was cloned in 1997.
• Carnitine-acylcarnitine translocase deficiency shares clinical features with other defects of long-chain fatty acid oxidation.
• The biochemical findings may be indistinguishable from the neonatal form of carnitine palmitoyltransferase type-2 deficiency.
• The mortality rate is high, and it occurs mainly in the first year of life.
• In at least a quarter of cases, patients show a mild presentation with long-term survival.
• Treatment consists of low-fat/high-carbohydrate diet and medium chain fat supplementation with frequent meals and avoidance of fasting.
Carnitine-acylcarnitine translocase (CACT) deficiency is a rare defect in mitochondrial long-chain fatty acid oxidation and was first described in 1992 (28). Fatty acid oxidation is a critical energy source during fasting, and defects commonly result in life-threatening energy deficiency. The process of long chain fatty acid oxidation requires esterifying the fatty acid to coenzyme A (forming an acylCoA), then exchanging the CoA for carnitine (forming an acylcarnitine), after which the enzyme carnitine-acylcarnitine translocase transports the acylcarnitine into the mitochondria where oxidation and energy production occur. There are approximately a dozen defects in long-chain fat metabolism, and they share similar clinical features related to their impairment of fasting, cardiac functioning, and skeletal muscle metabolism (30).
This disorder is rare, with only about 100 cases reported. The majority of patients become symptomatic in the newborn period. The mortality rate reaches up to 65% of patients in the first year of life due to cardiac complications (19). However, some patients have been described with later onset (03) or a milder phenotype and long-term survival (29). Evidence suggests that survival may be possible, even in some severe cases (25).
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