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Hereditary spherocytosis
Classification and external resources
ICD-10 D58.0
ICD-9 282.0
OMIM 182900
DiseasesDB 5827
eMedicine med/2147
MeSH D013103

Hereditary spherocytosis is a genetically-transmitted (autosomal dominant) form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than donut-shaped, and therefore more prone to hemolysis.[1]

Contents

Symptoms

As in non-hereditary spherocytosis, the spleen's hemolysis results in observational symptoms of fatigue, pallor, and jaundice.

Diagnosis

In a peripheral blood smear, the abnormally small red blood cells lacking the central pallor as seen in non-hereditary spherocytosis is typically more marked in hereditary spherocytosis.

Other protein deficiencies cause hereditary elliptocytosis, pyropoikilocytosis or stomatocytosis.

In longstanding cases and in patients who have taken iron supplementation or received numerous blood transfusions, iron overload may be a significant problem, being a potential cause of cardiomyopathy and liver disease. Measuring iron stores is therefore considered part of the diagnostic approach to hereditary spherocytosis.

An osmotic fragility test can aid in the diagnosis.[2]

Pathophysiology

Hereditary spherocytosis is an autosomal dominant or recessive trait,[3] most commonly (though not exclusively) found in Northern European and Japanese families, although an estimated 25% of cases are due to spontaneous mutations. A patient has a 50% chance of passing the mutation onto his/her offspring.

Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for spectrin (alpha and beta), ankyrin,[4] band 3 protein, protein 4.1,[5] and other erythrocyte membrane proteins. These proteins are necessary to maintain the normal shape of an erythrocyte, which is a biconcave disk. The integrating protein that is most commonly defective is ankyrin which is responsible for incorporation and binding of spectrin, thus in its dysfunction cytoskeletal instabilities ensue. As the spleen normally targets abnormally shaped red cells (which are typically older), it also destroys spherocytes. In the spleen, the passage from the cords of Billroth into the sinusoids may be seen as a bottleneck, where erythrocytes need to be flexible in order to pass through. In hereditary spherocytosis, erythrocytes fail to pass through and get phagocytosed, causing extravascular hemolysis. [6]

Treatment

As in non-hereditary spherocytosis, acute symptoms of anemia and hyperbilirubinemia indicate treatment with blood transfusions or exchanges and chronic symptoms of anemia and splenomegaly indicate dietary supplementation of folic acid and splenectomy,[7] the surgical removal of the spleen.

Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

Children with spherocytosis require immunization against the pneumococcus bacterium and prohylactic antibiotic treatment as well to decrease the risk of sepsis.

Prevalence

It is the most common (1 in 2,000 of Northern European ancestry) disorder of the red cell membrane.

See also

References

  1. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. pp. 625. ISBN 0-7216-0187-1. 
  2. ^ Won DI, Suh JS (March 2009). "Flow cytometric detection of erythrocyte osmotic fragility". Cytometry B Clin Cytom 76 (2): 135–41. doi:10.1002/cyto.b.20448. PMID 18727072. 
  3. ^ Eber S, Lux SE (April 2004). "Hereditary spherocytosis--defects in proteins that connect the membrane skeleton to the lipid bilayer". Semin. Hematol. 41 (2): 118–41. doi:10.1053/j.seminhematol.2004.01.002. PMID 15071790. http://linkinghub.elsevier.com/retrieve/pii/S0037196304000034. 
  4. ^ Gallagher PG, Forget BG (December 1998). "Hematologically important mutations: spectrin and ankyrin variants in hereditary spherocytosis". Blood Cells Mol. Dis. 24 (4): 539–43. doi:10.1006/bcmd.1998.0217. PMID 9887280. http://linkinghub.elsevier.com/retrieve/pii/S1079-9796(98)90217-0. 
  5. ^ Perrotta S, Gallagher PG, Mohandas N (October 2008). "Hereditary spherocytosis". Lancet 372 (9647): 1411–26. doi:10.1016/S0140-6736(08)61588-3. PMID 18940465. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61588-3. 
  6. ^ Chapter 12, page 425 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  7. ^ Bolton-Maggs PH, Stevens RF, Dodd NJ, Lamont G, Tittensor P, King MJ (August 2004). "Guidelines for the diagnosis and management of hereditary spherocytosis". Br. J. Haematol. 126 (4): 455–74. doi:10.1111/j.1365-2141.2004.05052.x. PMID 15287938. 

External links

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