What is hereditary spherocytosis?

Quick Answer
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.
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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 ANK1 gene, 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 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.


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