Hereditary elliptocytosis (HE) encompasses a heterogeneous group of red blood cell membrane disorders caused by mutations affecting the erythrocyte membranes and cytoskeletal proteins. Most patients are asymptomatic while those with the more severe forms of HE exhibit significant hemolytic anemia.
Hereditary elliptocytosis (HE) is comprised of red blood cell (RBC) membrane disorders that differ genetically, biochemically, and clinically  . The elliptically shaped erythrocytes in HE develop as a result of mutations in genes encoding αlpha-spectrin, beta-spectrin, or cytoskeletal proteins such as band 4.1 and glycophorin   . Hence, the defective membrane scaffolding leads to less RBC resilience and deformability. Of importance, the severity of the disease is correlated with the cell's surface area loss .
There are three morphologic variants of HE: common HE, spherocytic elliptocytosis, and Southeast Asian ovalocytosis, which are all inherited in an autosomal dominant pattern  . Note that there is a severe subtype of common HE, known as hereditary pyropoikilocytosis (HPP), which exhibits an autosomal recessive mode of inheritance .
While more than 90% of patients with HE are asymptomatic, the clinical presentation is variable depending on the type  . Common HE, the predominant form, is typically clinically silent. If the hemolysis is significant, patients will display symptoms related to anemia.
HPP features hemolytic anemia in infants typically of African origin . These patients continue to have hemolytic anemia throughout life. Another subtype of common HE, neonatal poikilocytosis, is observed in African American neonates and infants, who manifest with significant hemolytic anemia that resolves during their first year.
Spherocytic elliptocytosis occurs in those with European ancestry and causes milder forms of hemolysis while Southeast Asian ovalocytosis is characterized by mild no or no hemolysis. The latter has a resistance to malaria.
The assessment for RBC membrane disorders includes the patient and family history, a full physical exam, and the appropriate investigations.
Key laboratory studies comprise a complete blood count (CBC), reticulocyte count, bilirubin, haptoglobin, lactate dehydrogenase (LDH), Coombs test, potassium, and a peripheral blood smear . Findings indicative of hemolysis include an elevated reticulocyte count, low levels of haptoglobin, and increased levels of LDH and indirect bilirubin.
In patients with HE, microscopic analysis of the peripheral blood will reveal approximately 25% elliptocytes although this is variable. Fragmented RBCs are also common  . Of note, there is no correlation between the proportion of elliptocytes and the degree of hemolysis.
The erythrocyte morphology of each form of HE varies. In patients with the subtype HPP, the smear reveals poikilocytes, microspherocytes, RBC fragments, as well as elliptocytes . Moreover, spherocytic elliptocytosis features the presence of both elliptocytes and spherocytes while Southeast Asian ovalocytosis is associated with elliptocytes characterized by a transverse slit that bisects the cell.
Another diagnostic method, gel electrophoresis, is used for identification of protein deficiencies and analysis of spectrin . Also, osmotic fragility is a useful test. In the typical form of HE, osmotic fragility is normal whereas it is elevated in cases with HPP and spherocytic elliptocytosis .
Osmotic gradient ektacytometry, the reference technique for diagnosing RBC membrane diseases, measures the deformability index (DI)  . Its availability is limited although the invention of new ektacytometers will help widen its use .