Trifunctional mitochondrial protein deficiency (Mitochondrial trifunctional protein deficiency) - Genes and HADHB HADHA.

Trifunctional deficiency mitochondrial protein is a rare disease in which the body processes certain fats for energy, particularly during periods of fasting.

Signs and symptoms of mitochondrial trifunctional protein deficiency may begin in childhood or later in life. The characteristics that occur during childhood include feeding difficulties, lethargy, hypoglycaemia, hypotonia and liver problems. Affected children also have high risk of serious heart problems, difficulty breathing, coma and sudden death. Signs and symptoms of disease can begin after infancy and include hypotonia, muscular pain, wasting of muscle tissue and peripheral neuropathy. These problems can be triggered by periods of fasting or by diseases such as viral infections. Sometimes this disease is confused with Reye syndrome.

This process is due to mutations in genes HADHA, located on the short arm of chromosome 2 (2p23) and HADHB, located on the short arm of chromosome 2 (2p23). These genes encode part of an enzyme complex called trifunctional mitochondrial protein. This enzyme plays complex functions in mitochondria. As the name suggests, the trifunctional mitochondrial protein contains three enzymes that perform each a different function. This enzyme complex is required to metabolize fatty acids of chain length. Fatty acids long chain are an important source of energy for the heart, muscles, liver and other tissues.

Mutations in genes associated HADHA or HADHB trifunctional deficient mitochondrial protein disrupt the three functions of this enzyme complex. Without enough of this enzyme complex, fatty acids long chain of food and body fat can not be metabolised. Consequently, these fatty acids are used to generate energy, which can lead to some of the characteristics of this disease, such as lethargy and hypoglycemia. Fatty acids or partially metabolised long chain fatty acids can also build up and damage the liver, heart and muscles. This abnormal accumulation leads to the other signs and symptoms of mitochondrial trifunctional protein deficiency.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with mitochondrial trifunctional protein deficiency, by complete PCR amplification of the exons of HADHA and HADHB genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).