Carnitine acylcarnitine translocase deficiency

Carnitine-acylcarnitine translocase deficiency
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Hypoglycemia, Hyperammonemia, Cardiomyopathy, Liver dysfunction
Complications	N/A
Onset	Neonatal
Duration	Lifelong
Types	N/A
Causes	Mutations in the SLC25A20 gene
Risks	N/A
Diagnosis	Genetic testing, Newborn screening
Differential diagnosis	N/A
Prevention	N/A
Treatment	Dietary management, Medium-chain triglyceride supplementation
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Carnitine-acylcarnitine translocase deficiency (CACT deficiency) is a rare metabolic disorder that affects the transport of long-chain fatty acids into the mitochondria for beta-oxidation. This condition is part of a group of disorders known as fatty acid oxidation disorders.

Pathophysiology

Carnitine-acylcarnitine translocase (CACT) is an essential protein located in the inner mitochondrial membrane. It facilitates the transport of long-chain acylcarnitines from the cytosol into the mitochondrial matrix, where they undergo beta-oxidation to produce energy. In CACT deficiency, mutations in the SLC25A20 gene lead to a dysfunctional translocase, resulting in impaired fatty acid oxidation. This causes an accumulation of long-chain fatty acids and acylcarnitines in the body, leading to energy deficiency and toxic effects on various organs.

Genetics

CACT deficiency is inherited in an autosomal recessive pattern. The SLC25A20 gene, located on chromosome 3, encodes the carnitine-acylcarnitine translocase protein. Mutations in this gene disrupt the normal function of the translocase, leading to the clinical manifestations of the disorder.

Clinical Presentation

The clinical presentation of CACT deficiency typically occurs in the neonatal period. Symptoms may include:

• Severe hypoglycemia
• Hyperammonemia
• Cardiomyopathy
• Liver dysfunction
• Muscle weakness
• Seizures

Diagnosis

Diagnosis of CACT deficiency is often made through newborn screening programs that detect elevated levels of acylcarnitines in the blood. Confirmatory diagnosis involves genetic testing to identify mutations in the SLC25A20 gene. Additional diagnostic tests may include:

• Blood tests to measure acylcarnitine profiles
• Liver function tests
• Echocardiogram to assess cardiac function

Management

Management of CACT deficiency focuses on preventing metabolic crises and providing adequate nutrition. Key aspects of treatment include:

• A low-fat, high-carbohydrate diet to reduce reliance on fatty acid oxidation
• Supplementation with medium-chain triglycerides (MCTs), which can be metabolized without the need for carnitine transport
• Avoidance of fasting and prolonged exercise
• Emergency protocols for managing metabolic decompensation

Prognosis

The prognosis for individuals with CACT deficiency varies depending on the severity of the condition and the effectiveness of management strategies. Early diagnosis and intervention can improve outcomes, but some individuals may experience significant complications, including developmental delays and organ damage.

See also

• Fatty acid oxidation disorder
• Carnitine palmitoyltransferase I deficiency
• Carnitine palmitoyltransferase II deficiency

External links

• Genetic Testing Registry: Carnitine-acylcarnitine translocase deficiency