Which of the following is the primary defect in hereditary spherocytosis?
A. Deficiency of pyruvate kinase in glycolysis
B. Abnormal hemoglobin polymerization under hypoxic conditions
C. Deficiency of spectrin or ankyrin in the red cell membrane
D. Glucose-6-phosphatase deficiency in the pentose phosphate pathway
Explanation
Hereditary Spherocytosis: Membrane Protein Defect
Key Point
Hereditary spherocytosis (HS) is caused by deficiencies in red cell membrane skeleton proteins, most commonly spectrin or ankyrin, leading to loss of membrane integrity and osmotic fragility.
Pathophysiology
The red cell membrane is supported by a cytoskeletal network of proteins linked to the lipid bilayer. In HS:
1.
Spectrin or ankyrin deficiency weakens the membrane skeleton
2.
RBCs lose biconcave shape and become spherical
3.
Spherocytes are osmotically fragile and lyse in hypotonic solutions
4.
Splenic macrophages recognize and destroy spherocytes → hemolysis
Eosin-5-maleimide (EMA) binding test: Reduced fluorescence (most sensitive modern test)
Peripheral smear: Spherocytes (dense, small RBCs lacking central pallor)
Reticulocytosis: Elevated (compensatory response)
High-YieldNEET PG
Spectrin and ankyrin are the two most commonly deficient proteins in HS. Defects in other membrane proteins (band 3, protein 4.2) are less common but also cause HS.
Clinical Pearl
Patients often present with neonatal jaundice, splenomegaly, and chronic hemolysis. Splenectomy is curative because the spleen is the primary site of spherocyte destruction.
