Hereditary Spherocytosis and Hereditary Elliptocytosis
(See also Overview of Hemolytic Anemia.)
Hereditary spherocytosis and hereditary elliptocytosis are congenital RBC membrane disorders. Symptoms, generally milder in hereditary elliptocytosis, include variable degrees of anemia, jaundice, and splenomegaly. Diagnosis requires demonstration of increased RBC osmotic fragility and a negative direct antiglobulin test. Rarely, patients < 45 yr with symptomatic disease require splenectomy.
Hereditary spherocytosis (chronic familial icterus; congenital hemolytic jaundice; familial spherocytosis; spherocytic anemia) is an autosomal dominant disease with variable gene penetrance. It is characterized by hemolysis of spheroidal RBCs and anemia.
Hereditary elliptocytosis (ovalocytosis) is a rare autosomal dominant disorder in which RBCs are oval or elliptical. Hemolysis is usually absent or slight, with little or no anemia; splenomegaly is often present.
Alterations in membrane proteins cause the RBC abnormalities in both disorders.
In hereditary spherocytosis, the cell membrane surface area is decreased disproportionately to the intracellular content. The decreased surface area of the cell impairs the flexibility needed for the cell to traverse the spleen’s microcirculation, causing intrasplenic hemolysis.
In hereditary elliptocytosis, genetic mutations result in weakness of the cytoskeleton of the cell, leading to deformation of the cell. The abnormally shaped RBCs are taken up and destroyed by the spleen.
In hereditary spherocytosis, symptoms and signs are usually mild. The anemia may be so well compensated that it is not recognized until an intercurrent viral illness, such as parvovirus infection, transiently decreases RBC production, causing an aplastic crisis. These episodes can be self-limited, resolving with resolution of the infection, while others require urgent treatment. Moderate jaundice and symptoms of anemia are present in severe cases. Splenomegaly is almost invariable but only rarely causes abdominal discomfort. Hepatomegaly may be present. Cholelithiasis (pigment stones) is common and may be the presenting symptom. Congenital skeletal abnormalities (eg, tower-shaped skull, polydactylism) occasionally occur. Although usually one or more family members have had symptoms, several generations may be skipped because of variations in the degree of gene penetrance.
In hereditary elliptocytosis, clinical features are similar to those of hereditary spherocytosis but tend to be milder.
Hereditary spherocytosis or hereditary elliptocytosis is suspected in patients with unexplained hemolysis (as suggested by the presence of anemia and reticulocytosis), particularly if splenomegaly, a family history of similar manifestations, or suggestive RBC indices are present.
In hereditary spherocytosis, because RBCs are spheroidal and the MCV is normal, the mean corpuscular diameter is below normal, and RBCs resemble microspherocytes. MCHC is increased. Reticulocytosis of 15 to 30% and leukocytosis are common. In hereditary elliptocytosis, the RBCs are typically elliptical or cigar-shaped; however, the clinical presentation is variable. Diagnosis is usually made by the presence of at least 60% elliptocytes on peripheral smear and a family history of similar disease.
If these disorders are suspected, the following tests are done:.
RBC osmotic fragility test, which mixes RBCs with varying concentrations of saline
RBC autohemolysis test, which measures the amount of spontaneous hemolysis occurring after 48 h of sterile incubation
Direct antiglobulin (direct Coombs) test, to rule out spherocytosis due to autoimmune hemolytic anemia
RBC fragility is characteristically increased, but in mild cases, it may be normal unless sterile defibrinated blood is first incubated at 37° C for 24 h. RBC autohemolysis is increased and can be corrected by the addition of glucose. The direct antiglobulin test results are negative.
Splenectomy, after appropriate vaccination, is the only specific treatment for hereditary spherocytosis or hereditary elliptocytosis but is rarely needed. It is indicated in patients with symptomatic hemolysis or complications such as biliary colic or persistent aplastic crisis. If the gallbladder has stones or other evidence of cholestasis, it should be removed during splenectomy. Although spherocytosis persists after splenectomy, the cells survive longer in the circulation. Usually, symptoms resolve and anemia and reticulocytosis decrease. However, RBC fragility remains high.