Mitochondrial Trifunctional Protein Deficiency

Mitochondrial trifunctional protein deficiency is an autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats to energy, particularly during periods without food . People with this disorder have inadequate levels of an enzyme that breaks down a certain group of fats called long-chain fatty acids.

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).

Genes related to Definency

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

Mutations 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.