Hydroxyacyl-CoA dehydrogenase long chain deficiency 3- ..., (LCHAD) (Long Chain hydroxyacyl-CoA dehydrogenase deficiency -LCHAD-) - Gen HADHA

Deficiency 3hydroxyacyl-CoA dehydrogenase long chain (LCHAD: Long Chain hydroxyacyl-CoA dehydrogenase deficiency) is a rare disorder that prevents organisms metabolize certain fats for energy, particularly during periods fasting.

Signs and symptoms of deficiency LCHAD usually occur in infancy or early childhood and may include feeding difficulties, lethargy, hypoglycemia, hypotonia, liver problems and anomalies in the retina. Later in childhood, those affected may exhibit muscle pain, breakdown of muscle tissue, and peripheral neuropathy. Individuals deficient LCHAD also at risk of serious heart problems, respiratory distress, coma and sudden death. LCHAD related problems can be triggered by periods of fasting or by diseases such as viral infections. Sometimes this condition is confused with Reye syndrome - see Reye 's syndrome -.

This process is due to mutations in the gene HADHA, located on the short arm of chromosome 2 (2p23). This gene encodes part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions fulfilled in mitochondria. As the name suggests, mitochondrial trifunctional protein contains the three enzymes that perform different functions each. This enzyme complex is required to metabolize fatty acids long chain. Fatty acids long chain found in foods such as milk and certain oils. These fatty acids are stored in the fatty tissue of the organism and are a major source of energy for the heart and muscles. During periods of fasting, the fatty acids are also an important source of energy for the liver and other tissues.

HADHA have identified several genetic mutations in people with deficient LCHAD. These mutations reduce the activity of 3-hydroxyacyl-CoA dehydrogenase , mitochondrial trifunctional enzyme protein the long chain. Other enzymatic activities of the protein are maintained at or near normal. Many of the mutations change HADHA amino acids used to encode the alpha subunit. The most common mutation replaces the amino acid glutamic acid for glutamine at amino acid position 474 in the alpha subunit (Glu474Gln or E474Q). The Glu474Gln mutation and other amino acid substitutions likely to alter the structure of the alpha subunit, preventing normal operation. Other mutations result in an abnormally short, nonfunctional version of the alpha subunit.

A deficiency of alpha functional subunits, inhibits the metabolism and processing of long chain fatty acids. Consequently, these fatty acids are converted to energy, which can lead to some of the characteristics of LCHAD, such as lethargy and hypoglycemia. In addition, fatty acids partly metabolised or long chain fatty acids can also build up and damage the liver, heart, muscles and retina. This abnormal accumulation leads to the other signs and symptoms of deficiency LCHAD.

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 deficiency of 3-hydroxyacyl-CoA dehydrogenase, long chain (LCHAD), by complete PCR amplification of exons HADHA gene, 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).