Carnitine-acylcarnitine translocase

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare, genetic metabolic disorder that affects the body's ability to convert certain fats into energy, particularly during periods without food (fasting). This condition is part of a group of disorders known as fatty acid oxidation disorders. Carnitine-acylcarnitine translocase is an essential protein located in the inner mitochondrial membrane, playing a critical role in the transport of long-chain fatty acids from the cytoplasm into the mitochondria for energy production.

Symptoms

The symptoms of CACT deficiency typically appear in the newborn period or early infancy and can include hypoglycemia (low blood sugar), hypotonia (reduced muscle tone), cardiomyopathy (heart muscle disease), liver dysfunction, and hyperammonemia (elevated levels of ammonia in the blood). If untreated, the disorder can lead to severe metabolic crisis, neurological damage, or death.

Causes

CACT deficiency is caused by mutations in the SLC25A20 gene, which provides instructions for making the carnitine-acylcarnitine translocase enzyme. This enzyme is crucial for the transport of long-chain fatty acids into the mitochondria, where they are broken down through a process called beta-oxidation to generate energy. Mutations in the SLC25A20 gene reduce or eliminate the function of this enzyme, leading to the accumulation of fatty acids in the body's tissues and preventing cells from utilizing fats for energy.

Diagnosis

Diagnosis of CACT deficiency involves a combination of clinical evaluation, biochemical tests, and genetic testing. Biochemical tests may show abnormal levels of carnitine and acylcarnitines in the blood, while genetic testing can identify mutations in the SLC25A20 gene.

Treatment

Treatment for CACT deficiency is aimed at preventing metabolic crises and involves dietary management to avoid fasting and restrict the intake of long-chain fatty acids. Medium-chain triglycerides (MCTs) are often used as an alternative energy source because they do not require carnitine for their transport into mitochondria. In addition, carnitine supplementation may be recommended to enhance the excretion of accumulated fatty acids. Management of this condition requires a multidisciplinary approach, including a metabolic geneticist, dietitian, cardiologist, and other healthcare professionals.

Prognosis

The prognosis for individuals with CACT deficiency varies. With early diagnosis and appropriate management, some individuals can lead relatively normal lives. However, the condition can be life-threatening in the absence of treatment, and even with treatment, individuals may experience metabolic crises, particularly during illness or fasting.