Hereditary spherocytosis
Hereditary spherocytosis is a genetic condition characterized by the abnormal shape and fragility of red blood cells, which take on a spherical form instead of the normal disc shape. This alteration in cell structure is primarily due to mutations in genes responsible for producing proteins that maintain the integrity of the red blood cell membrane, most commonly the ANK1 gene. The spherical red blood cells are prone to premature destruction in the spleen, leading to symptoms such as jaundice, anemia, fatigue, and in children, irritability. The condition can affect individuals of all ethnic backgrounds, but it is most prevalent among those of Northern European descent.
Symptoms can vary from mild to severe, with some cases diagnosed in childhood and others not identified until adulthood. Diagnosis typically involves a medical history review, physical examination, and specific blood tests. Treatment options focus on managing symptoms and may include folic acid supplementation, blood transfusions, and in some cases, surgical removal of the spleen, which can alleviate anemia despite not correcting the cell shape. As hereditary spherocytosis is an inherited disorder, it is important for families with a history of the condition to undergo regular screening to ensure early detection and management.
Hereditary spherocytosis
ALSO KNOWN AS: Congenital spherocytic anemia
DEFINITION Spherocytosis is a condition that causes an abnormality in the red blood cell membrane. While healthy blood cells are shaped like flattened, indented disks, these abnormal membranes lead to sphere-shaped red blood cells and to the premature breakdown of those cells. Red blood cells suffering from spherocytosis are smaller, rounder in shape, and more fragile than healthy red blood cells. The rounded shape causes the red blood cells to be caught in the spleen, where they break down.
Spherocytosis occurs in all races, but is most common in people of northern European descent, affecting 1 in 2,000 members of that population according to the US National Library of Medicine's Genetic Home Reference in 2014. Spherocytosis cases may be very mild, with minor symptoms, or very severe, with symptoms that quickly surface. These symptoms may occur after certain types of infections. Severe cases may be diagnosed in childhood, while patients with mild symptoms may not be diagnosed until adulthood. With treatment, symptoms can be controlled.
Risk Factors
Having a family member with spherocytosis increases an individual’s risk of developing the condition.
Etiology and Genetics
Most cases of hereditary spherocytosis result from a mutation in the ANK1gene, found on the short arm of chromosome 8 at position 8p11.21. This gene encodes the ankyrin protein, which is a major cell membrane protein found on the surface of erythrocytes (red blood cells). Ankyrin is believed to interconnect with protein molecules called alpha spectrin and beta spectrin, which are major components of the erythrocyte cytoskeleton. The reduction or loss of ankyrin molecules on the cell surface distorts this cytoskeleton, causing the cells to assume the spherical shape characteristic of the disease. Mutations in the alpha spectrin gene, erythrocytic 1 (SPTA1, at position 1q21) or beta spectrin gene, erythrocytic (SPTB, at position 14q24.1–q24.2) are also known to cause erythrocytes to be spherical and thus result in symptoms associated with spherocytosis. Finally, rare cases of hereditary spherocytosis have been associated with mutations in two other genes that encode structural protein components of the erythrocyte cytoskeleton: solute carrier family 4 (anion exchanger), member 1 (Diego blood group) (SLC4A1 at position 17q21.31) and erythrocyte membrane protein band 4.2 (EPB42 at position 15q15–q21).
Spherocytosis resulting from mutations in the SPTA1 gene is inherited as an autosomal recessive disorder, but all other varieties of the disease are inherited in an autosomal dominant fashion. In autosomal recessive inheritance, both copies of the SPTA gene must be deficient in order for the individual to be afflicted. Typically, an affected child is born to two unaffected parents, both of whom are carriers of the recessive mutant allele. The probable outcomes for children whose parents are both carriers are 75 percent unaffected and 25 percent affected. In autosomal dominant inheritance, however, a single copy of the mutation is sufficient to cause full expression of the syndrome. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Many cases of dominant hereditary spherocytosis, however, result from a spontaneous new mutation, so in these instances affected individuals will have unaffected parents.
Symptoms
Symptoms of spherocytosis include jaundice, pallor, shortness of breath, fatigue, and weakness. Symptoms in children include irritability and moodiness. Additional symptoms include hemolytic anemia and gallstones.
Screening and Diagnosis
The doctor will ask about a patient’s symptoms and medical history and will perform a physical exam. Tests may include an examination of the spleen; blood tests; liver function tests; osmotic and incubated fragility tests to diagnose hereditary spherocytosis; and Coombs’ test, an antiglobulin test to examine red blood cell antibodies.
Treatment and Therapy
Patients should talk with their doctors about the best plans for them. Among treatment options, a daily 1-milligram dose of folic acid and consideration for blood transfusions are recommended during periods of severe anemia.
Surgical removal of the spleen can cure the anemia. The abnormal shape of blood cells remain, but the blood cells are no longer destroyed in the spleen. Currently, meningococcal, Haemophilus, and pneumococcal vaccines are administered several weeks before splenectomy. Lifetime penicillin prophylaxis is recommended after surgery to prevent dangerous infections. The surgery is not recommended for children under the age of five. There is a lifetime risk of serious and potentially life-threatening infections.
Prevention and Outcomes
Because spherocytosis is an inherited condition, it is not possible to prevent the disease. Regular screening of individuals at high risk, however, can prevent the risk of complications of the disease with early treatment.
Bibliography
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Gallagher, Patrick G. “Disorders of the Red Cell Membrane: Hereditary Spherocytosis, Elliptocytosis, and Related Disorders.” Williams Hematology. Ed. Marshall A. Lichtman et al. 7th ed. New York: McGraw, 2006. Print.
Genetics Home Reference. "Hereditary Spherocytosis." Genetics Home Reference. US NLM, 21 July 2014. Web. 25 July 2014.
Gersten, Todd. "Congenital Spherocytic Anemia." MedlinePlus. US NLM/NIH, 24 Feb. 2014. Web. 25 July 2014.
Kalfa, Theodosia A., Jessica A. Connor, and Amber H. Begtrup. "EPB42-Related Hereditary Spherocytosis." GeneReview. Ed. Roberta A. Pagon et al. Seattle: U of Washington, Seattle, 1993–2014. NCBI Bookshelf. Natl. Center for Biotechnology Information. 13 Mar. 2014. Web. 25 July 2014.
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Tracy, Elisabeth T., and Henry E. Rice. “Partial Splenectomy for Hereditary Spherocytosis.” Pediatric Hematology. Eds. Max J. Coppes and Russell E. Ware. Philadelphia: Saunders, 2008. Print.
Wu, Yangyang, Lin Liao and Faquar Lin. "The Diagnosis Protocol for Hereditary Spherocytosis--2021 Update." Journal of Clinical Laboratory Analysis, 24 Oct. 2021, doi.org/10.1002/jcla.24034. Accessed 4 Sept. 2024. Zamora, Edgar A., et al. "Hereditary Spherocytosis, National Library of Medicine, 4 July 2023, www.ncbi.nlm.nih.gov/books/NBK539797/. Accessed 4 Sept. 2024.