Q65.Sickle cell anemia causes sickling of the RBCs. Which of the following is not correct for the disease?
A. Haemoglobin forms large aggregates.
B. Disease does not affect the oxyhaemoglobin but decreases solubility of deoxyhaemoglobin.
C. The enhanced aggregation propensity is due to the hydrophobic effect of the underlying mutation.
D. The patients are more prone to malaria.
E. The disease is not curable.
Choose the correct answer from the options given below:
(1) A, B, C Only
(2) C, D, E Only
(3) D, E Only
(4) B, C Only
Sickle cell anemia involves deoxyhemoglobin S polymerization due to a Glu→Val mutation, but it affects both oxy and deoxy forms differently. The correct answer is option (4): B, C only—these statements are incorrect.
Statement Evaluation
A. Haemoglobin forms large aggregates. Correct—deoxy-HbS polymerizes into 14-strand fibers, distorting RBCs into sickle shapes.
B. Disease does not affect the oxyhaemoglobin but decreases solubility of deoxyhaemoglobin. Incorrect—while deoxy-HbS solubility drops dramatically (polymerizes at >15 g/dL), oxy-HbS also shows reduced solubility and forms aggregates under high concentration, unlike normal HbA.
C. The enhanced aggregation propensity is due to the hydrophobic effect of the underlying mutation. Correct explanation but technically imprecise—the β6 Glu→Val mutation creates a hydrophobic “sticky patch” enabling lateral HbS contacts, but aggregation requires T-state (deoxy) conformation, not pure hydrophobic effect.
D. The patients are more prone to malaria. Correct—heterozygotes (HbAS) resist falciparum malaria; homozygotes (HbSS) have complex protection during crises despite higher susceptibility.
E. The disease is not curable. Correct in exam context—while bone marrow transplant cures, it’s not routine; gene therapies emerging but standard care remains symptomatic.
Option Analysis
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(1) A, B, C Only: Wrong—B incorrect.
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(2) C, D, E Only: Wrong—C better classified correct.
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(3) D, E Only: Incomplete—misses B/C.
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(4) B, C Only: Correct—the two technically flawed statements.
Sickle cell anemia causes sickling of the RBCs through HbS polymerization, but not all listed statements hold. The β6 Glu→Val mutation creates a hydrophobic Val patch on deoxy-HbS, forming fibers that rigidify RBCs.
Key Mechanisms
Deoxygenation shifts HbS to T-state, exposing Val-β6 for intermolecular contacts—solubility plummets 50-fold vs HbA. Fibers distort biconcave RBCs into sickles, causing vaso-occlusion.
Incorrect Claims
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Oxyhemoglobin unaffected: False—oxy-HbS aggregates at high phosphate (>1.5M), unlike HbA.
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Pure hydrophobic effect: Imprecise—requires specific T-state geometry beyond simple hydrophobicity.
Clinical Notes
HbAS protects against malaria; HbSS patients face chronic hemolysis, crises. Curable via transplant, managed with hydroxyurea.
Exam Focus
NEET/CSIR tests mutation specifics—B/C fail mechanistic precision.
