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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.
Pathophysiology
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.
Symptoms and Signs
Symptoms and signs of hereditary spherocytosis are usually mild, and the anemia may be so well compensated that it is not recognized until an intercurrent viral illness transiently decreases RBC production, simulating an aplastic crisis. However, these episodes are self-limited, resolving with resolution of the infection. 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.
Clinical features of hereditary elliptocytosis are similar to those of hereditary spherocytosis but tend to be milder.
Diagnosis
These disorders are suspected in patients with unexplained hemolysis, particularly if splenomegaly, a family history of similar manifestations, or suggestive RBC indices are present. 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.
If these disorders are suspected, the RBC osmotic fragility test (which mixes RBCs with varying concentrations of saline), the RBC autohemolysis test (which measures the amount of spontaneous hemolysis occurring after 48 h of sterile incubation), and, to rule out spherocytosis due to autoimmune hemolytic anemia, the direct antiglobulin (Coombs') test are done. 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.
Treatment
Splenectomy, after appropriate vaccination, is the only specific treatment for either disorder but is rarely needed. It is indicated in patients < 45 yr with Hb persistently < 10 g/dL, jaundice or 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.
Last full review/revision February 2009 by Alan E. Lichtin, MD
Content last modified February 2012
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