LCHAD Deficiency

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. People with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency have inadequate levels of an enzyme required for a step that metabolizes a group of fats called long-chain fatty acids.

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), muscle weakness (hypotonia), liver problems, and abnormalities in the part of the eye that detects light and color (the retina). Muscle pain, breakdown of muscle tissue, and abnormalities in the nervous system that affect arms and legs (peripheral neuropathy) may occur later in childhood. Individuals with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are also at risk for complications such as life-threatening heart and breathing problems, coma, and sudden unexpected death.

Problems related to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.


Causes

Mutations in the HADHA gene cause long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.

Mutations in the HADHA gene lead to inadequate levels of an enzyme called long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, which is part of a protein complex known as mitochondrial trifunctional protein. Long-chain fatty acids from food and body fat cannot be metabolized and processed without sufficient levels of this enzyme. As a result, these fatty acids are not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, retina, and muscles, causing more serious complications.