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Hereditary spherocytosis


Other Names:
Congenital spherocytic hemolytic anemia; Congenital spherocytosis; Spherocytic anemia
Categories:
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]
Last updated: 6/19/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Increased red cell osmotic fragility 0005502
30%-79% of people have these symptoms
Cholelithiasis
Gallstones
0001081
Hepatomegaly
Enlarged liver
0002240
Hyperbilirubinemia
High blood bilirubin levels
0002904
Hypercoagulability 0100724
Hypofibrinogenemia 0011900
Increased mean corpuscular hemoglobin concentration 0025548
Jaundice
Yellow skin
Yellowing of the skin
[ more ] 		0000952
Muscle weakness
Muscular weakness
0001324
Pallor 0000980
Reticulocytosis
Increased immature red blood cells
Increased number of immature red blood cells
[ more ] 		0001923
Spherocytosis 0004444
Splenomegaly
Increased spleen size
0001744
Spontaneous hemolytic crises 0005525
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain
[ more ] 		0002027
Ataxia 0001251
Chills 0025143
Extramedullary hematopoiesis 0001978
Fever 0001945
Maculopapular exanthema 0040186
Myalgia
Muscle ache
Muscle pain
[ more ] 		0003326
Restrictive cardiomyopathy 0001723
1%-4% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating
[ more ] 		0003270
Gout 0001997
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
Skin ulcer
Open skin sore
0200042
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance 0000006
Autosomal recessive inheritance 0000007
Hemolytic anemia 0001878
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Last updated: 7/1/2020
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]
Last updated: 4/26/2016
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]
Last updated: 4/26/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
The treatment of hereditary spherosytosis (HS) is dependent on the severity of the condition and recommendations vary a bit in the medical literature. In general, folate therapy (a type of vitamin B to support red blood cell production) is recommended for those with moderate to severe anemia, although some doctors may also recommend it for those with mild anemia. Red blood cell transfusions may be required in severe cases of anemia, particularly in the first years of life or during infections and pregnancy. If red blood cell transfusions are needed repeatedly, iron chelating therapy may be required to reduce iron overload.[4][5][6]

Regular monitoring for anemia and gallstones is advised. Removal of the spleen (splenectomy) is usually only performed in severe HS or in moderate to severe cases with significant anemia and gallstone complications. Splenectomy is not recommended in cases of mild HS except in specific cases. The majority of medical researchers no longer recommend that the spleen be removed during gallbladder removal (cholecystectomy), unless there are other reasons to do so. In some cases only removing of part of the spleen is advised. Expert evaluation is recommended in order to avoid unnecessary spleen removal.[4][5][6]
Last updated: 11/17/2016
Overall, the long-term outlook (prognosis) for people with hereditary spherocytosis (HS) is usually good with treatment.[7] However, it may depend on the severity of the condition in each person. HS is often classified as being mild, moderate or severe.[5] People with very mild HS may not have any signs or symptoms unless an environmental "trigger" causes symptom onset.[4] In many cases, no specific therapy is needed other than monitoring for anemia and watching for signs and symptoms.[8] Moderately and severely affected people are likely to benefit from splenectomy.[5] Most people who undergo splenectomy are able to maintain a normal hemoglobin level.[4] However, people with severe HS may remain anemic post-splenectomy, and may need blood transfusions during an infection.[5]

Information about life expectancy in the medical literature appears to be limited. However, we are not aware of reports that state that life expectancy is known to be significantly shortened in people without other medical problems who are managed appropriately. In all people who undergo splenectomy, there is a lifelong, increased risk of developing a life-threatening infection (sepsis).[9] Although most septic episodes have been observed in children whose spleens were removed in the first years of life, older children and adults also are susceptible. Fortunately, taking certain precautions can reduce this risk and can prevent minor infections from becoming life-threatening.[9] 
Last updated: 4/27/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include hereditary elliptocytosis, hereditary stomatocytosis, Southeast Asian ovalocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, autoimmune hemolytic anemia, and alpha-thalassemia (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Hereditary spherocytosis. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Hereditary spherocytosis. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hereditary spherocytosis. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • I was 37 when I was diagnosed. I had my spleen and gallbladder removed. The last two years I find myself getting really tired and fall asleep for a few minutes to feel recharged. Will this continue to get worse? My concern is with driving and at work. I also would like any information on the long term effects of hereditary spherocytosis. Is there any increased risk of strokes or heart attacks? And is there any effect on life expectancy? Any information on this would be greatly appreciated. I cannot find much about it anywhere. See answer

  • Does hereditary spherocytosis (and splenectomy) have any effect on pregnancy? See answer

  • My son has hereditary spherocytosis and I am trying to learn more about it. Are their any restrictions that I should be aware of, such as dietary or physical activities? See answer

  • I have hereditary spherocytosis and I have a son that has it too. He had a splenectomy when he was almost 3 and he is 7 now. He is on penicillin every day. I have been told by his doctor (not a hematologist) that he doesn't have to be on the medicine anymore. Is that correct? Also, is there a chance my other unaffected kids can give this disorder to their kids? See answer

  • Is there research that demonstrates the long term effects of removal of spleen and gallbladder in children with hereditary spherocytosis? How do these procedures affect their future health?  What are the chances of this disease being passed to my child's future children? See answer

  • Can Soliris be used to cure hereditary spherocytosis? See answer

  • What causes hereditary spherocytosis? How can I learn about research on this topic? In particular I'm interested in learning more about the role of genetics and possible links to radiation or drug exposure. See answer


  1. Hereditary spherocytosis. Genetics Home Reference. September, 2013; http://ghr.nlm.nih.gov/condition/hereditary-spherocytosis.
  2. Hemolytic anemia. MedlinePlus. January 19, 2018; https://medlineplus.gov/ency/article/000571.htm.
  3. Hereditary Spherocytosis. Seattle Children's. http://www.seattlechildrens.org/medical-conditions/heart-blood-conditions/hereditary-spherocytosis/. Accessed 6/19/2018.
  4. Gus Gonzalez. Hereditary Spherocytosis. Medscape Reference. October 13, 2015; http://emedicine.medscape.com/article/206107-overview.
  5. Bolton-Maggs PH, Langer JC, Iolascon A, Tittensor P, King MJ and General Haematology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis and management of hereditary spherocytosis. British Journal of Haematology. January 2012; 156(1):37-49. http://www.ncbi.nlm.nih.gov/pubmed/22055020.
  6. Mentzer WC. Hereditary spherocytosis: Clinical features, diagnosis, and treatment. UpToDate. May 3 2016; http://www.uptodate.com/contents/hereditary-spherocytosis-clinical-features-diagnosis-and-treatment.
  7. Congenital spherocytic anemia. MedlinePlus. February 24, 2014; https://www.nlm.nih.gov/medlineplus/ency/article/000530.htm.
  8. What is hereditary spherocytosis?. Children's Minnesota. https://www.childrensmn.org/services/care-specialties-departments/cancer-blood-disorders/conditions-and-services/blood-disorders-services/hemoglobinopathy-sickle-cell/hs/. Accessed 4/24/2016.
  9. Mark S Pasternack. Patient information: Preventing severe infection after splenectomy (Beyond the Basics). UpToDate. March, 2016; http://www.uptodate.com/contents/preventing-severe-infection-after-splenectomy-beyond-the-basics.