X-Linked Sideroblastic Anaemia

What is X-linked sideroblastic anaemia?

X-linked sideroblastic anaemia is an inherited disorder that prevents red blood cells from making sufficient haemoglobin, the iron-containing protein that carries oxygen in the blood. Although these blood cells are supplied with an adequate amount of iron, they are less able to use it to make haemoglobin. Iron that is not incorporated into haemoglobin 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 during the first three decades of life. 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 these increased levels of iron.

How common is X-linked sideroblastic anaemia?

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

What genes are related to X-linked sideroblastic anaemia?

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

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

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

People who inherit a mutation in a second gene, the HFE gene, along with a mutation in the ALAS2 gene may experience more severe signs and symptoms of this disorder. Other mutations in the HFE gene cause haemochromatosis, which is another type of iron overload disorder.

How do people inherit X-linked sideroblastic anaemia?

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.

What other names do people use for X-linked sideroblastic anaemia?

  • anaemia, hereditary sideroblastic
  • anaemia, sex-linked hypochromic sideroblastic
  • ANH1
  • Congenital sideroblastic anaemia
  • Erythroid 5-aminolevulinate synthetase deficiency
  • Hereditary iron-loading anaemia
  • Hypochromic anaemia
  • X-linked pyridoxine-responsive sideroblastic anaemia
  • XLSA

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