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Disease Profile

Hereditary spherocytosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

All ages

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ICD-10

D58.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Congenital spherocytic hemolytic anemia; Congenital spherocytosis; Spherocytic anemia

Categories

Blood Diseases; Congenital and Genetic Diseases

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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.

    Treatment

    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]

    Organizations

    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

      Learn more

      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

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • MedlinePlus Genetics contains information on Hereditary spherocytosis. This website is maintained by the National Library of Medicine.
      • 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.

          References

          1. Hereditary spherocytosis. Genetics Home Reference. September, 2013; https://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. https://www.seattlechildrens.org/medical-conditions/heart-blood-conditions/hereditary-spherocytosis/. Accessed 6/19/2018.
          4. Gus Gonzalez. Hereditary Spherocytosis. Medscape Reference. October 13, 2015; https://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. https://www.ncbi.nlm.nih.gov/pubmed/22055020.
          6. Mentzer WC. Hereditary spherocytosis: Clinical features, diagnosis, and treatment. UpToDate. May 3 2016; https://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; https://www.uptodate.com/contents/preventing-severe-infection-after-splenectomy-beyond-the-basics.

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