The sideroblastic anemias are a group of blood disorders in which the body has enough iron but is unable to use it to make hemoglobin, which carries oxygen in the blood. As a result, iron accumulates in the mitochondria of red blood cells, giving a ringed appearance to the nucleus (ringed sideroblast). There are three categories of sideroblastic anemias: inherited, acquired, and idiopathic (of unknown origin). The signs and symptoms can range from mild to severe, and include fatigue, breathing difficulties, and weakness. Enlargement of the liver or spleen may also occur. In severe cases, the increased levels of iron in the blood may lead to heart disease, liver damage, and kidney failure.
The sideroblastic anemias are characterized by fatigue, breathing difficulties, and feelings of weakness. On exertion, persons with this disorder may feel angina-like chest pains.
The more common forms of anemia are caused by iron deficiencies in the blood. People with sideroblastic anemias have abnormally high levels of iron and iron-containing substances in the blood serum. In some cases, the mucous membranes and the skin of hands and arms of persons with sideroblastic anemia may look pale, often lemon-yellow colored. Rarely, a brownish red discoloration caused by bleeding under the skin may occur.
Enlargement of the spleen (splenomegaly) or liver (hepatomegaly) are other symptoms of these disorders. Acute leukemia develops in fewer than 10% of cases, as a complication of advanced sideroblastic anemias.
Hereditary sideroblastic anemia is the result of a defect in an X-linked recessive gene. The gene, known as ALAS2, makes an enzyme that is essential in the production of ‘heme’, the oxygen-carrying portion of the hemoglobin molecule. The defective gene is located on the X chromosome (Xp11.21).
X-linked sideroblastic anemia usually becomes apparent at some point during the first three decades of life.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome Xp11.21” refers to band 11.21 on the short arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is turned off and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is ‘turned off’. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
Acquired sideroblastic anemia is the result of prolonged exposure to certain toxic substances or drugs, or an unpleasant effect of other disorders such as immune disorders, granulomatous disease, tumors, or metabolic disorders.
As the name suggests, the cause of idiopathic sideroblastic anemia is not known.
Hereditary sideroblastic anemia affects both men and women, but is more common among males. The onset of this form of the disorder usually occurs before age 30, although cases have been diagnosed in patients over 70 years of age.
Acquired sideroblastic anemia is more often seen among older patients of either sex, usually at age 65 or older. However, patients have been diagnosed in their mid-50s.
Suspicion of an occurrence of sideroblastic anemia will generate blood studies including staining of the red blood cells to determine if the characteristic ringed sideroblasts are present in the mitochondria. Biochemical analyses may be conducted to determine the level of an enzyme essential to hemoglobin, delta-aminolevulinic synthetase.
Treatment depends on the cause of the sideroblastic anemia. If the disorder is acquired, the responsible agent must be identified and avoided.
Vitamin B6 (pyridoxine) therapy may be helpful in some cases.
To remove excess iron from the body of someone with sideroblastic anemia, the drug desferrioxamine (Desferal) is infused under the skin (subcutaneously) or injected into a muscle (intramuscular), often with good results. Desferrioxamine binds excess iron and promotes its excretion from the body.
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Yamamoto M, Harigae H. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:373-74.
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:860-61.
Larson DE, ed. Mayo Clinic Family Health Book. New York, NY: William Morrow and Company, Inc; 1996:963.
Hoffman R, Benz Jr EJ, Shattil SJ et al., eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:545-52.
Ferreira GC, Zhang JS. Mechanism of 5-amnolevulinate synthase and the role of the protein environment in controlling the cofactor chemistry. Cell Mol Biol (Noisy-le-grand). 2002;48:827-33.
Drysdale J, Arosio P, Invernizzi R, et al. Mitochondrial ferritin: a new player in iron metabolism. Blood Cells Mol Dis. 2002;29:376-83.
Greenberg PL, Young NS, Gattermann N. Myelodysplastic syndromes. Hematology (Am Soc Hematol Educ Program). 2002;:136-61.
Fleming MD. The genetics of inherited sideroblastic anemias. Semin Hematol. 2002;39:270-81.
McLintock LA, Fitzsimons EJ. Erythroblast iron metabolism in sideroblastic and sideropenic states. Hematology. 2002;7:189-95.
Furuyama K, Sassa S. Multiple mechanisms for hereditary sideroblastic anemia. Cell Mol Biol (Noisy-le-grand) 2002;48:5-10.
Alcindor T, Bridges KR. Sideroblastic anemias. Br J Haematol. 2002;116:733-43.
Kaplan J. Spinocerebellar ataxias due to mitochondrial defects. Neurochem Int. 2002;40:553-57.
Andrews NC. Iron metabolism: iron deficiency and iron overload. Annu Rev Genomics Hum Genet. 2000;1:75-98.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Anemia, Sideroblastic, X-linked. Entry Number; 301300: Last Edit Date; 3/17/2004.
X-linked sideroblastic anemia. Genetics Home Reference. Last Comprehensive Review: June 2004, Published: January 7, 2005. 3pp.
ALAS2 (Aminolevulinate,delta,synthase2 (sideroblastic/hypochromic anemia). Genetics Home Reference. Published: January 7, 2005. 3pp.
HFE (Hemochromatosis). Genetics Home Reference. Published: January 7, 2005. 3pp.
Alcindor T, Bridges KR. Sideroblastic Anemias. Revised January 19, 2001. 15pp.
Sideroblastic Anemia. Iron Disorders Institute. Last Updated: 11/03/2004. 4pp.
Sideroblastic anemia. Orphanet. June 1999. 1p.
Greenberg PL, Young NS, Gattermann N. Myelodysplastic Syndromes. Hematology 2002. 37pp.
Haggerty M. Sideroblastic anemia. Health A to Z. December, 2002. 3pp.
Iron deficiency anemia. Mayo Clinic. June 16, 2003. 6pp.
Conrad ME. Anemia. emedicine. Last Updated: September 29, 2004. 21pp.
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