Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Acetyl coenzyme A medium chain deficiency ... (Medium-chain dehydrogenase deficiency acylCoA- -MCAD-) - Gen ACADM.

Deficiency acetyl coenzyme A medium chain (MCAD deficiency) is an alteration that prevents the body to convert certain fats in energy, especially fasting.

Signs and symptoms of this disorder usually appear during infancy or early childhood and may include vomiting, lethargy and hypoglycemia. In rare cases, symptoms of the disease first appear during adulthood. People with MCAD deficiency are at risk for serious complications, such as seizures, difficulty breathing, liver problems, brain damage, coma and sudden death. Problems can be triggered by periods of fasting or by diseases such as viral infections.

This process is due to mutations in the gene ACADM, located on the short arm of chromosome 1 (1p31), encoding an enzyme called medium chain acyl CoA dehydrogenase, which is required to decompose the fatty acid medium chain. Fatty acids are an important 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.

There are more than 80 mutations in the gene causing ACADM acetyl coenzyme A deficient medium chain. Many of these mutations change amino acids in the MCAD enzyme. The most common change replaces the amino acid lysine for glutamic acid at amino acid position 304 of the enzyme (Lys304Glu or K304E). This mutation and other amino acid substitutions alter the structure of the enzyme, reducing or eliminating its activity significantly. Other mutations lead to an abnormally small and unstable enzyme nonfunctional. Without sufficient amounts of this enzyme, fatty acid medium chain they are not metabolized properly. As a result, lethargy and hypoglycemia can occur. Fatty acid medium chain fatty acids or partially metabolized, can also accumulate in tissues and damage the liver and brain.

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 acetyl coenzyme A deficient medium chain by complete PCR amplification of the exons of the gene ACADM, 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).