Hereditary Spherocytosis

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Chapter 452 Hereditary Spherocytosis

Hereditary spherocytosis is a common cause of hemolysis and hemolytic anemia, with a wide spectrum of severity and with a prevalence of approximately 1/5,000 in people of Northern European descent. It is the most common inherited abnormality of the red blood cell (RBC) membrane. Affected patients may be asymptomatic, without anemia and with minimal hemolysis, or they may have severe hemolytic anemia. Hereditary spherocytosis has been described in most ethnic groups but is most common among persons of Northern European origin.

Etiology

Hereditary spherocytosis usually is transmitted as an autosomal dominant or, less commonly, as an autosomal recessive disorder. As many as 25% of patients have no previous family history. Of these patients, most represent new mutations, and a few cases result from recessive inheritance or represent nonpaternity. The most common molecular defects are abnormalities of spectrin or ankyrin, which are major components of the cytoskeleton responsible for RBC shape. A recessive defect has been described in α-spectrin. Dominant defects have been described in β-spectrin and protein 3. Dominant and recessive defects have been described in ankyrin (Table 452-1). A deficiency in spectrin, protein 3, or ankyrin results in uncoupling in the “vertical” interactions of the lipid bilayer skeleton and the loss of membrane microvesicles (Figs. 452-1 and 452-2). The loss of membrane surface area without a proportional loss of cell volume causes sphering of the RBCs and an associated increase in cation permeability, cation transport, adenosine triphosphate (ATP) use, and glycolysis. The decreased deformability of the spherocytic RBCs impairs cell passage from the splenic cords to the splenic sinuses, and the spherocytic RBCs are destroyed prematurely in the spleen. Splenectomy markedly improves RBC life span and cures the anemia.

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Figure 452-2 Pathophysiologic effects of hereditary spherocytosis.

(From Perrotta S, Gallagher PG, Mohandas N: Hereditary spherocytosis, Lancet 372:1411–1426, 2008.)