This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
What is Hereditary Spherocytosis?
Hereditary spherocytosis is a condition in which red blood cells (RBCs) are shaped as spheres, rather than the normal toroidal “donut” shape. This abnormal shape leads to premature breakdown of RBCs, which in turn leads to hemolytic anemia. [1] Anemia can accompany other health concerns such as frequent gallstones, jaundice, and enlargement of the spleen (Splenomegaly, see below). These conditions can affect individuals with a range of severity, and symptoms can lessen in severity with age. [2] The short video below gives a visual of how the misshapen blood cells can lead to such symptoms.
Splenomegaly
The change in RBC shape also causes the cells to be more fragile and less flexible. [3] As a result, many of them burst when the blood is being filtered through the spleen, which in turn can lead to enlargement of the spleen. It is possible to remove the spleen wholly or partially, however there has been some controversy as to whether this is a good idea or not. In some cases it may be medically necessary or may help to reduce gallstone production and anemic symptoms. However, it has also been proven that patients with hereditary spherocytosis who do no not undergo a splenectomy are at a lower risk for vascular disease than even healthy family members. [4]
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How is Spherocytosis inherited?
Hereditary Spherocytosis is usually inherited in an autosomal dominant pattern (see Figure 1), but less commonly is also inherited recessively (see Figure 2). [2] This means that the gene responsible for Spherocytosis is located on a non-sex chromosome in all cases. Dominant inheritance means that only one copy of the affected gene is required to pass on the disease. When it is inherited recessively, it's possible that neither parent shows symptoms but are both carriers of the disease gene. If this is the case, a child has a 25% chance of having the disease since both parents must pass on the mutant gene.
The chances of inheriting Spherocytosis are also dependent on ethnicity. Cases in people of Northern European descent occur with a frequency of 1 in 2000, but are much less common in other ethnic backgrounds. [2]
The chances of inheriting Spherocytosis are also dependent on ethnicity. Cases in people of Northern European descent occur with a frequency of 1 in 2000, but are much less common in other ethnic backgrounds. [2]
Inheritance Patterns Explained
ANK1
There are at least five genes where mutations have been found to lead to spherocytosis, however the culprit approximately half of the time is the ANK1 gene.
References
Cover Image: http://pedsinreview.aappublications.org/content/suppl/2001/06/27/22.7.219.DC1/020-003aHereditary_Spherocytosis_smear.jpg
1. A.D.A.M Medical Encyclopedia. (Reviewed February 8, 2012) Congenital Spherocytic Anemia. Retrieved Feb 3, 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001557/
2. Genetics Home Reference. (Reviewed October, 2010) Hereditary Spherocytosis. Retrieved Feb 3, 2013. http://ghr.nlm.nih.gov/condition/hereditary-spherocytosis
3. University of Virginia School of Medicine. Membrane Disorders. Retrieved Feb 3, 2013. http://www.med-ed.virginia.edu/courses/path/innes/rcd/membrane.cfm
4. Schilling, RF. (2009) Risks and benefits of splenectomy versus no splenectomy for hereditary spherocytosis--a personal view. British Journal of Haematology, 145, 728-732. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/19388926
5. Image created by Bethany Zeitler
1. A.D.A.M Medical Encyclopedia. (Reviewed February 8, 2012) Congenital Spherocytic Anemia. Retrieved Feb 3, 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001557/
2. Genetics Home Reference. (Reviewed October, 2010) Hereditary Spherocytosis. Retrieved Feb 3, 2013. http://ghr.nlm.nih.gov/condition/hereditary-spherocytosis
3. University of Virginia School of Medicine. Membrane Disorders. Retrieved Feb 3, 2013. http://www.med-ed.virginia.edu/courses/path/innes/rcd/membrane.cfm
4. Schilling, RF. (2009) Risks and benefits of splenectomy versus no splenectomy for hereditary spherocytosis--a personal view. British Journal of Haematology, 145, 728-732. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/19388926
5. Image created by Bethany Zeitler