Hereditary Spherocytosis/Hereditary Ellipocytosis (ANK1, SPTB, SPTA1, SLC4A1, EPB42)

Clinical Features

Hereditary spherocytosis (HS), also known as Minkowski-Chauffard disease, affects 1 in 2,000 individuals. HS is a condition in which red blood cells lose their typical biconcave disc shape and appear spherical. The spherical appearance impairs membrane flexibility making it hard for red blood cells to transverse narrow capillaries, especially in the spleen. This impairment causes anemia due to chronic extravascular hemolysis, jaundice, formation of bilirubin gallstones, reticulocytosis, and splenomegaly characteristic of HS disease (Aster et al., 2013. An X, Mohandas N. 2008. PubMed ID: 18341630). Disease severity can range with 20-30% having mild form, 60-70% having moderate form, and 10-20% having severe form of HS. People with mild forms may be asymptomatic whereas severe forms of the disease present in newborns with life threatening anemia and require blood transfusions. There are five types of HS defined by the gene mutation causative for disease: Type 1-ANK1, type 2-SPTB, type 3-SPTA1, type 4-SLC4A1, and type 5-EPB42 (Bolton-Maggs et al., 2012. PubMed ID: 22055020; Delaunay J. 2007.PubMed ID: 16730867).

Hereditary elliptocytosis (HE) is a milder red blood cell membrane disorder affecting 1 in 5,000 individuals. Red blood cells in these patients are elongated into cigar or oval shape with flexibility being impaired less than individuals with HS. The majority of patients are asymptomatic with ~10% having moderate to severe anemia and intermittent episodes of hemolysis, jaundice, and splenomegaly. Symptoms may present at 4-6 months in severe cases but usually resolve by 6-12 months. Severe HE may present with hereditary pyropoikilocytosis with newborns presenting with hemolytic anemia and requiring frequent blood transfusions. Elliptocytosis may be prominent in other disorders including iron deficiency, leukemia, megaloblastic anemia, myelofibrosis, sickle cell disease, thalassemia, and polycythemia. Therefore, genetic testing is helpful in differential diagnosis of these diseases (Gallagher P.G. 2004. PubMed ID: 15071791).


Therapeutic intervention for HS/HE varies, but treatment options include folate supplements, total/partial splenectomy, and/or regular transfusions (Seims et al., 2013. PubMed ID: 24074424). Genetic sequencing helps to determine erythrocyte membrane protein gene mutations associated with HS or HE (Bolton-Maggs et al., 2012. PubMed ID: 22055020).


Splenectomy has been a treatment for patients diagnosed with HS and severe HE but has not typically been used on young children (Bolton-Maggs et al., 2012. PubMed ID: 22055020). In severe forms of HS/HE, splenectomies are performed to avoid blockage of splenic vasculature due to the abnormal red blood cell morphology. Most cases are curative and minimize hemolytic anemia through this process (Bolton-Maggs et al., 2012. PubMed ID: 22055020). In mild and asymptomatic cases of HS, splenectomy has been used to prevent gallstone formations. Partial splenectomies have been utilized, selectively in children, to decrease hemolysis while maintaining immunity. Possible disadvantages of partial splenectomies compared to total splenectomies include heightened hemolysis and risk for anemia. (Seims et al., 2013. PubMed ID: 24074424).

Blood Transfusions

Studies have shown leukodepleted blood transfusions, which limit risk of alloimmune reactions, are typically reserved for children with early onset (children diagnosed before the age of 6), due to an inability of their bone marrow to combat impaired red blood cell numbers. Transfusion dependence, according to clinical studies, is estimated to range between 70-80% of HS-affected infants within the first year of life (Tchernia et al., 2000. PubMed ID: 11920183 ).

Folic Acid Supplements

Young children (pre and post-operational) have benefited from folate supplements (Vitamin B9) in order to help generate healthy red blood cells and reduce symptoms of folic acid deficiencies. Folate replacement tends to be routine for children with severe hemolysis and for pregnant women. (Bolton-Maggs et al., 2004. PubMed ID: 15287938).


This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.

Last Updated: 10/3/2017