Hereditary spherocytosis

Hereditary spherocytosis is a condition characterized by hemolytic anemia (when red blood cells are destroyed earlier than normal). Signs and symptoms can range from mild to severe and may include pale skin, fatigue, anemia, jaundice, gallstones, and/or enlargement of the spleen.^[1] Other symptoms of hemolytic anemia may include feeling that your heart is pounding or racing (palpitations), feeling dizzy, problems concentrating, and headaches.^[2][3] Some people with a severe form of hereditary spherocytosis may have short stature, delayed puberty, and skeletal abnormalities. The condition is caused by mutations in any of several genes, such as the ANK1, EPB42, SLC4A1, SPTA1, and SPTB genes. It is most commonly inherited in an autosomal dominant manner, but may be inherited in an autosomal recessive manner. There are different types of hereditary spherocytosis, which are distinguished by severity and genetic cause.^[1] Depending on severity, treatment may involve splenectomy, red cell transfusions, folic acid supplementation, and/or cholecystectomy.^[4]

Hereditary spherocytosis may be caused by changes (mutations) in any of several genes. These genes give the body instructions to make proteins that exist on the membranes of red blood cells. These proteins carry molecules in and out of cells, keep cell structure, and attach to other proteins. Some increase the flexibility of cells so they can easily travel from larger blood vessels to smaller, narrow blood vessels.

The gene mutations that cause hereditary spherocytosis cause red blood cells to have an abnormal, spherical shape with decreased flexibility. The misshapen red blood cells are called spherocytes. The spherocytes are taken out of circulation and sent to the spleen to be destroyed (hemolysis). This results in a shortage of red blood cells in the blood, and too many in the spleen.^[1]

About half of all cases of hereditary spherocytosis are due to mutations in the ANK1 gene. Other genes associated with the condition include the EPB42, SLC4A1, SPTA1, and SPTB genes.^[1]

About 75% of cases of hereditary spherocytosis are inherited in an autosomal dominant manner.^[1] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Less commonly, hereditary spherocytosis is inherited in an autosomal recessive manner.^[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% (1 in 4) chance to be affected
• 50% (1 in 2) chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not be a carrier

In some of the cases that result from new mutations in people with no family history of the condition, the inheritance pattern may be unclear.^[1]

Currently there is no evidence to suggest that radiation or drug exposure causes hereditary spherocytosis.

The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. You can view information about clinical trials relating to hereditary spherocytosis here. Use the study’s contact information to learn more. Check this site often for regular updates. 

You can also contact the Patient Recruitment and Public Liaison (PRPL) Office at the National Institutes of Health (NIH). We recommend calling 1-800-411-1222 to speak with a specialist, who can help you determine if you are eligible for any clinical trials. If you are located outside the United States, and would like to be contacted via telephone, you will need to contact PRPL and provide your telephone number in full, including area code and international dialing prefix. 

Patient Recruitment and Public Liaison Office 
NIH Clinical Center 
Bethesda, Maryland 20892-2655 
Toll-free: 1-800-411-1222 
Fax: 301-480-9793 
E-mail: prpl@mail.cc.nih.gov 
Web site: http://clinicalcenter.nih.gov 

You can find information about participating in a clinical trial as well as learn about resources for travel and lodging assistance, through the Get Involved in Research section of our Web site.