ALAS2

The ALAS2 gene provides instructions for the production of an enzyme called delta-aminolevulinate synthase 2 (ALA-synthase). ALAS2 is one of two genes that carry instructions for making this enzyme. The ALAS2 gene makes a version of ALA-synthase that is produced only in developing red blood cells (sideroblasts). The other gene that makes this enzyme, ALAS1, is turned on in all tissues in the body. ALA-synthase carries out a step in the production of heme, the iron-containing part of hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. The activity of ALA-synthase determines how much heme, and therefore how much hemoglobin, will be produced by red blood cells.

Heme production is a multistep process, and each step is controlled by a different enzyme. The first step in the production of heme is the manufacture of a compound called delta-aminolevulinic acid (ALA), which is achieved through the action of ALA-synthase. Seven other enzymes will modify this compound before it becomes heme. The heme molecule is then incorporated into hemoglobin and packaged into red blood cells.

X-linked sideroblastic anemia - caused by mutations in the ALAS2 gene

More than 25 mutations that cause X-linked sideroblastic anemia have been identified in the ALAS2 gene. These mutations prevent the normal production of heme and result in reduced levels of hemoglobin in the blood. Because there is not enough hemoglobin to incorporate iron, excess iron builds up in sideroblasts. The signs and symptoms of X-linked sideroblastic anemia are a result of low hemoglobin levels and a buildup of iron in the body's tissues.