Carnitine-acylcarnitine translocase deficiency
Carnitine-acylcarnitine translocase (CACT) deficiency is a rare genetic condition that prevents the body from using certain fats for energy, particularly during periods without food. This disorder can lead to life-threatening complications, with symptoms often appearing shortly after birth.
Overview
Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Many infants with CACT deficiency do not survive the newborn period. However, some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals remain at risk for liver failure, nervous system damage, coma, and sudden death.
Symptoms
Signs and symptoms of CACT deficiency usually begin soon after birth and can include:
- Breathing problems
- Seizures
- An irregular heartbeat (arrhythmia)
- Low blood glucose (hypoglycemia) combined with a low level of ketones (hypoketotic hypoglycemia)
- Excess ammonia in the blood (hyperammonemia)
- An enlarged liver (hepatomegaly)
- A weakened heart muscle (cardiomyopathy)
Frequency
CACT deficiency is a very rare disorder; at least 30 cases have been reported in medical literature.
Causes & Genetic Factors
Mutations in the SLC25A20 gene cause CACT deficiency. This gene provides instructions for making a protein called carnitine-acylcarnitine translocase (CACT). This protein is essential for fatty acid oxidation, a multistep process that breaks down (metabolizes) fats and converts them into energy inside the mitochondria (the energy-producing centers in cells).
A group of fats called long-chain fatty acids must be attached to a substance known as carnitine to enter the mitochondria. Once joined, the CACT protein transports them inside. Fatty acids are a major source of energy for the heart and muscles, and they serve as an important energy source for the liver and other tissues during fasting.
Mutations in the SLC25A20 gene alter the structure of the CACT protein, leading to a shortage (deficiency) of the transporter. Without enough functional CACT protein, long-chain fatty acids cannot be transported into the mitochondria to be converted into energy. This reduced energy production leads to features like hypoketotic hypoglycemia. Additionally, fatty acids and long-chain acylcarnitines (fatty acids still attached to carnitine) can build up in cells, damaging the liver, heart, and muscles, which causes the other signs and symptoms of the disorder.
Associated Gene
- SLC25A20
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- CACT deficiency
- Carnitine acylcarnitine translocase deficiency
- Carnitine-acylcarnitine carrier deficiency