Inherited Disorders Of The Erythrocytes: Hereditary Spherocytosis As A Red Cell Membrane Disorder

Hereditary spherocytosis is the most common inherited disorder of erythrocyte membrane. It is an autosomal dominant disorder presenting as a chronic hemolytic anemia with the presence of spherocytes in peripheral blood, Intermittent jaundice and splenomegaly. In 80% of cases, family history indicates hereditary involvement.

Pathogenesis

Though the exact molecular lesion in spherocytosis is yet unknown, several alterations in structure and function of the cell membrane have been noticed. These include

1. Reduction in membrane lipid;
2. Increased permeability to sodium; and
3. Defective phosphorylation of the membrane protein-spectrin.

The spherocytes are erythrocytes which assume a spherical shape due to inability to maintain the normal biconcave shape. Spleen destroys the defective erythrocytes. Bone marrow shows erythroid hyperplasia. In long standing cases, gall stones are common.

Clinical Manifestations

The condition presents in the second and third decades with mild hemolytic anemia and recurrent jaundice. Many cases remain asymptomatic throughout life. Hemolytic and aplastic crises may occur from time to time. Extreme cases may present as neonatal hyperbilirubinemia needing exchange transfusion.

Laboratory findings

Hemoglobin level is usually 8-10 g/dl. Reticulocyte count ranges from 5-20%. Over 30% of erythrocytes in the peripheral blood are spherocytes. They are smaller in diameter, thicker and appear uniformly stained with loss of the central pallor. Mean corpuscular volume is increased. The osmotic fragility is increased because of the red cell spheroidicity. Autohemolysis occurs in stored blood and this is corrected by the addition of glucose or ATP, Coomb’s test is negative.

Diagnosis

Recurrent anemia, jaundice, splenomegaly and spherocytosis should suggest this diagnosis, though spherocytosis may occur in other types of hemolytic anemias also. Occurrence of spherocytosis and hemolysis in siblings or parents strengthens the diagnosis. In addition, demonstration of autohemolysis and its correction by glucose or ATP are diagnostic, since these tests are specific for hereditary spherocytosis.

Treatment

Hereditary spherocytosis is functionally curable by splenectomy in almost all cases. Poor response to splenectomy or relapse suggests a wrong diagnosis or the development of accessory splenic tissue. Children have a higher tendency to develop pneumococcal and other types of septicemia after splenectomy and, therefore, splenectomy should be avoided in children below 5-10 years of age. In some intractable cases, splenectomy may have to be done but this should be followed by prophylactic penicillin therapy and pneumococcal vaccination when indicated.