Hereditary spherocytosis

Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, a hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than donut-shaped, and therefore more prone to hemolysis.

This article covers aspects of spherocytosis specific to the hereditary form of the disorder. See that article for details that apply generally to this variant as well as others.

Symptoms

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

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. See the article on spherocytosis for details.

Other hereditary morphological variants of red blood cells include hereditary elliptocytosis, pyropoikilocytosis and 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.

Pathophysiology

Hereditary spherocytosis is an autosomal dominant trait, 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 disorder onto his/her offspring, presuming that his/her partner does not also carry the mutation.

Hereditary spherocytosis is caused by a variety of molecular defects in the genes that code for spectrin, ankyrin, protein 4.1, and other erythrocyte membrane proteins. These proteins are necessary to maintain the normal shape of an erythrocyte, which is a biconcave disk. The protein that is most commonly defective is ankyrin. As the spleen normally targets abnormally shaped red cells (which are typically older), it also destroys spherocytes.

Hereditary spherocytosis is associated with thromboembolic disease. 15/15 spherocytic mice showed signs of thrombosis in one 1997 study. A 1997 case report discussed the relationship between arterial thrombosis and hereditary spherocytosis

Treatment

Acute symptoms of anemia or hyperbilirubinemia require treatment with blood transfusions or exchange transfusions. Chronic symptoms of anemia and splenomegaly may necessitate splenectomy, the surgical removal of the spleen. Pharmacological or dietary iron supplementation may not be useful if the patient has iron overload. See the article on spherocytosis for details.

Gene therapy using retroviral vectors to correct hereditary spherocytosis has been successful in vitro; human trials have not been attempted as of February 2007.

Prevalence

It is the most common (1 in 5,000 of Northern European ancestry) disorder of the red cell membrane.

See also

• Spherocytosis
• Anemia
• Hematology

External links

• Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 182900. World Wide Web URL: http://omim.org/.
• A short article from WebMD
• A picture of spherocytes from Medline
• A detailed and technical (but good) article from eMedicine

References

• Kumar, Vinay, Abul Abbas, and Nelson Fausto. "Robbins and Cotran Pathologic Basis of Disease, 7th edition (2004)."
• Schneider, Arthur S. and Philip A. Stanzo. "Board Review Series: Pathology, 2nd edition (2002)."