X-linked sideroblastic anemia

X-linked sideroblastic anemia is an inherited disorder that prevents red blood cells (erythrocytes) from making sufficient hemoglobin, the iron-containing protein that carries oxygen in the blood. In X-linked sideroblastic anemia, red blood cells cannot use iron efficiently to make hemoglobin. As a result, the body tries to compensate by absorbing more iron from the diet. Iron that is not incorporated into hemoglobin builds up in other tissues and organs in the body, where it can cause damage.

The signs and symptoms of this disorder range from mild to severe and usually begin by the age of 30. The characteristic features of this disorder include pale skin, fatigue, dizziness, and an enlarged spleen and liver. Heart disease, liver damage, and kidney failure are severe medical problems that can result from the buildup of iron in these organs.

This form of anemia is very rare; several hundred cases have been reported worldwide.

Mutations in the ALAS2 gene cause X-linked sideroblastic anemia.

Mutations in the HFE gene modify the course of X-linked sideroblastic anemia.

The ALAS2 gene provides instructions for making an enzyme called ALA-synthase, which is critical in the chemical process that leads to heme production. Heme is part of the hemoglobin protein and is vital for supplying oxygen to the entire body. When the ALAS2 gene is mutated, heme cannot be produced normally. As a result, not enough hemoglobin is made, allowing iron to build up and damage the body's tissues.

People who inherit mutations in the HFE gene, along with a mutation in the ALAS2 gene, may experience particularly severe signs and symptoms of X-linked sideroblastic anemia. Mutations in the HFE gene can also lead to increased absorption of iron from the diet and result in hemochromatosis, which is another type of iron overload disorder. A more serious iron overload can occur from the combined effect of these two mutations on iron absorption.

Read more about the ALAS2 and HFE genes.

This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. Some females with one altered copy of the ALAS2 gene may exhibit some signs and symptoms related to this condition. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.