Ketothiolase deficiency ... (Beta ketothiolase deficiency) - Gen ACAT1.

Ketothiolase deficiency is a hereditary disorder in which the body can not process effectively isoleucine. This alteration also impairs the body's ability to process molecules produced during the decomposition of fats.

Signs and symptoms of the disease usually appear between 6 months and 24 months old. Affected children have episodes of vomiting, dehydration, difficulty breathing, lethargy and sometimes seizures. These episodes, called ketoacidotic attacks, sometimes leading to coma. Ketoacidotic attacks are often triggered by infections, periods of fasting, or an increased intake of foods rich in protein.

This process is due to mutations in the gene ACAT1, located on the long arm of chromosome 11 (11q22.3), which encodes an enzyme found in mitochondria. This enzyme plays an essential role in the breakdown of proteins and fats in the diet. More specifically, the enzyme processing aid isoleucine produced during decomposition of fats. Isoleucine in processing a molecule called 2-methyl-acetoacetylCoA becomes two smaller, propionyl-CoA and acetyl-CoA, which can be used to produce energy molecules. The enzyme performs the final step in the decomposition of ketone for the transformation of fats. The enzyme converts a molecule called acetoacetylCoA two molecules of acetyl-CoA, which can be used to produce energy. In the liver, the enzyme also performs this chemical reaction in reverse, that is the first step in the construction of new ketones.

They have identified more than 40 mutations in the gene ACAT1 in people with ketothiolase deficiency. Mutations in the gene reduce or eliminate the activity of the enzyme. The lack of this enzyme prevents the body to process proteins and fats correctly. As a result, the related compounds may accumulate to toxic levels in the blood. These substances cause the blood to become too acidic and can damage the tissues and organs of the body, particularly the nervous system. This damage causes episodes of vomiting, dehydration and other health problems associated with the disease.

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 ketothiolase, by complete PCR amplification of the exons of the gene ACAT1, 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).