Mitochondrial trifunctional protein deficiency

Mitochondrial trifunctional protein 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 mitochondrial trifunctional protein deficiency have inadequate levels of an enzyme required for three steps that metabolize a group of fats called long-chain fatty acids.

Onset of mitochondrial trifunctional protein deficiency may begin during infancy or later in life. Signs and symptoms that occur during infancy include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), muscle weakness (hypotonia), and liver problems. Infants with this disorder are also at high risk for complications such as life-threatening heart and breathing problems, coma, and sudden unexpected death. Characteristic features of mitochondrial trifunctional protein deficiency that begins after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and abnormalities in the nervous system that affect arms and legs (peripheral neuropathy).

Problems related to mitochondrial trifunctional protein 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.

Mitochondrial trifunctional protein deficiency is a rare disorder; its incidence is unknown.

Mutations in the HADHA and HADHB genes cause mitochondrial trifunctional protein deficiency.

Mutations in the HADHA and HADHB genes can lead to inadequate levels of an enzyme 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 complex. 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, and muscles, causing more serious complications.

Read more about the HADHA and HADHB genes.

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.