X-linked Sideroblastic Anaemia
What else is it called?
- Anaemia, hereditary sideroblastic
- Anaemia, sex-linked hypochromic sideroblastic
- Congenital sideroblastic anaemia
- Erythroid 5-aminolevulinate synthase deficiency
- Hereditary iron-loading anaemia
- X chromosome-linked sideroblastic anaemia
- X-linked pyridoxine-responsive sideroblastic anaemia
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What causes it?
X-linked Sideroblastic Anaemia is caused by mutations (changes) in the ALAS2 gene. This gene provides instructions for making an enzyme called erythroid ALA-synthase which plays an important role in the production on heme (a part of the haemoglobin protein) in the bone marrow.
Mutations in the ALAS2 gene disrupts the activity of erythroid ALA-synthase and therefore also disrupts the normal production of heme, preventing erythroblasts from making enough haemoglobin. Normally, all the iron transported into erythroblasts is incorporated into heme. The reduced production of heme causes a build-up of excess iron in these cells. The body tries to make up for the shortage of haemoglobin by absorbing more iron from the diet. This collection of excess iron damages the organs in the body. The low haemoglobin levels and build-up of iron in the organs lead to the symptoms associated with this condition.
In rare cases, individuals may have a mutation in another gene (HFE) as well as a mutation in the ALAS2 gene leading to a more severe form of XLSA. The combined effects of both these mutations can lead to a more serious iron overload.
How common is it?
XLSA is a very rare inherited disorder. The exact prevalence is unknown but an estimate of 200 cases have been reported to date.
What are the signs and symptoms?
The signs and symptoms of this condition can range from mild to severe and most commonly, symptoms first appear in young adulthood. Common features include:
- Fatigue (extreme tiredness)
- A rapid heartbeat
- Pale skin
- Hepatosplenomegaly (an enlarged liver and spleen)
Over time, the build-up of excess iron in the organs may lead to:
- Heart disease
- Cirrhosis (liver damage)
Other, more rarely seen symptoms include:
- Hyperglycaemia (high blood glucose levels)
- Glucose intolerance
- Skin hyperpigmentation (a condition in which patches of skin become darken in colour than the surrounding skin)
How is it diagnosed?
A diagnosis is made based on identifying characteristic symptoms, a detailed patient history, clinical evaluation and a range of specialized tests.
Tests that may be done to determine a diagnosis include, a full blood count, reticulocyte count (blood test measuring how fast red blood cells called reticulocytes are made by the bone marrow and released into the blood), measurement of iron stores and a bone marrow biopsy.
The diagnosis can be confirmed through mutation analysis of the ALAS2 gene.
Can it be treated?
XLSA may respond to treatment with vitamin B6 (pyridoxine) and folic acid. In cases where the individual is unresponsive to this and the anaemia is severe, red cell transfusions are necessary. Chelation therapy (a medical procedure that removes heavy metals from the body) is used to treat Iron overload.
Do my family need to be tested?
X-linked Sideroblastic Anaemia is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.
The inheritance pattern of this condition is an X-linked recessive pattern. The gene linked to this condition is located on the X chromosome, one of the two sex chromosomes. In males (who only have one X chromosome), one changed cope of the gene in each cell is enough to cause the condition. In females (who have two X chromosomes), a change would have to occur in both copies of the gene in order to cause the disorder. Males are therefore affected by the condition more frequently than females as it is unlikely that females will have two changed copies of this gene. A characteristic of this inheritance pattern is that fathers cannot pass X-linked traits to their sons.
In disorders with an X-linked recessive inheritance pattern, a female with one changed copy of the gene in each cell is known as a carrier. A carrier of an ALAS2 gene mutation can pass on the mutated gene but most people do not develop any symptoms associated with the condition. Although there are no symptoms present, carriers may have abnormally small, pale red blood cells that can be detected through a blood test.