Organic Acidemias Health Article

Definition

Organic acidemias are a collection of amino and fatty acid oxidation disorders that cause non-amino organic acids to accumulate and be excreted in the urine.

Description

Organic acidemias are divided into two categories: disorders of amino acid metabolism and disorders involving fatty acid oxidation. There are several dozen different organic acidemia disorders. They are caused by inherited deficiencies in specific enzymes involved in the breakdown of branched-chain amino acids, lysine, and tryptophan, or fatty acids. Some have more than one cause.

Amino acids are chemical compounds from which proteins are made. There are about 40 amino acids in the human body. Proteins in the body are formed through various combinations of roughly half of these amino acids. The other 20 play different roles in metabolism. Organic acidemias involving amino acid metabolism disorders include isovaleric acidemia, 3-methylcrotonylglycemia, combined carboxylase deficiency, hydroxymethylglutaric acidemia, propionic acidemia, methylmalonic acidemia, beta-ketothiolase deficiency, and glutaric acidemia type I.

Fatty acids, part of a larger group of organic acids, are caused by the breakdown of fats and oils in the body. Organic acidemias caused by fatty acid oxidation disorders include glutaric acidemia type II, short-chain acyl-CoA dehydrogenase (SCAD) deficiency, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, long-chain acyl-CoA dehrdrogenase (LCAD) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency.

Most organic acidemias are considered rare, occurring in less than one in 50,000 persons. However, MCAD occurs in about one in 23,000 births. Most of these disorders produce life-threatening illnesses that can occur in newborns, infants, children, and adults. In nearly all cases, though, the symptoms appear during the first few years of life, usually in children age two or younger. If left undiagnosed and untreated in young children, they can also delay physical development.

Genetic profile

Genes are the blueprint for the human body, directing the development of cells and tissue. Mutations in some genes can cause genetic disorders such as the organic acidemias. Every cell in the body has 23 pairs of chromosomes, 22 pairs of which contain two copies of individual genes. The twenty-third pair of chromosomes is called the sex chromosome because it determines a person's gender. Men have an X and a Y chromosome while women have two X chromosomes.

Organic acidemias are generally believed to be autosomal recessive disorders that affect males and females. Autosomal means that the gene does not reside on the sex chromosome. People with only one abnormal gene are carriers but since the gene is recessive, they do not have the disorder. Their children will be carriers of the disorder 50% of the time but not show symptoms of the disease. Both parents must have one of the abnormal genes for a child to have symptoms of an organic acidemia. When both parents have the abnormal gene, there is a 25% chance each child will inherit both abnormal genes and have the disease. There is a 50% chance each child will inherit one abnormal gene and become a carrier of the disorder but not have the disease itself. There is a 25% chance each child will inherit neither abnormal gene and not have the disease nor be a carrier.

Demographics

Organic acidemias affect males and females roughly equally. The disorders primarily occur in Caucasian children of northern European ancestry, such as English, Irish, German, French, and Swedish. In a 1994 study by Duke University Medical Center, 120 subjects with MCAD were studied. Of these, 118 were Caucasian, one was black, and one was Native American; 65 were female and 55 were male; and 112 were from the United States while the other eight were from Great Britain, Canada, Australia, and Ireland.