**Question:** Which of the following statements about Hemoglobin S (HbS) is not true?

A. Hemoglobin S is a type of hemoglobin found in individuals with sickle cell disease.
B. Hemoglobin S causes the red blood cells to lose their ability to carry oxygen.
C. Hemoglobin S is a normal variant of hemoglobin found in individuals from certain African, Asian, and Mediterranean populations.
D. The presence of two abnormal hemoglobin genes is required for sickle cell disease to develop.

**Correct Answer:** C. Hemoglobin S is a normal variant of hemoglobin found in individuals from certain African, Asian, and Mediterranean populations.

**Core Concept:** Hemoglobin S (HbS) is a naturally occurring hemoglobin variant that alters the structure of red blood cells (RBCs). In healthy individuals with two normal hemoglobin gene copies (HbA), HbS accounts for approximately 10%-15% of RBCs. However, in individuals with sickle cell disease, the presence of a single abnormal hemoglobin S gene leads to the production of sickle hemoglobin (HbS), which results in the formation of abnormal RBCs with a sickle shape. This abnormal shape causes the RBCs to become rigid, sticky, and prone to rupture, leading to a range of clinical manifestations in sickle cell disease.

**Why the Correct Answer is Right:** The statement "Hemoglobin S is a normal variant of hemoglobin found in individuals from certain African, Asian, and Mediterranean populations" is incorrect because HbS is not a normal variant in these populations. It is rather a genetic mutation, specifically a single abnormal hemoglobin S gene, that results in the production of sickle hemoglobin (HbS) leading to sickle cell disease. The statement may be true for carriers of the gene, but it does not apply to affected individuals with the disease.

**Why Other Answers are Incorrect:**

A. Hemoglobin S is a type of hemoglobin found in individuals with sickle cell disease: This answer is incorrect because HbS is not a type of hemoglobin but a variant that alters the structure of RBCs, leading to sickle cell disease.

B. Hemoglobin S causes the red blood cells to lose their ability to carry oxygen: This answer is incorrect because HbS does not directly affect the RBCs' oxygen-carrying capacity. However, the abnormal shape of RBCs in sickle cell disease does impair their ability to function effectively in delivering oxygen.

D. The presence of two abnormal hemoglobin S genes is required for sickle cell disease: This answer is incorrect because a single HbS gene can lead to the production of sickle hemoglobin (HbS) and result in sickle cell disease. The disease is inherited as an autosomal recessive trait, meaning that if an individual has one normal and one mutated HbS gene, they are considered an HbS carrier, not a sickle cell disease patient.

**Clinical Pearls:**

- Sickle cell disease occurs when an individual inherits one normal and one mutated HbS gene, leading to the production of sickle hemoglobin and the formation of

✓ Correct Answer: C. Binding of HbS to the deoxygenated HbA can extend the polymer and cause sickling of the red blood cells