**Question:** A 37-year-old factory worker develops increasing weakness in the legs; coworkers have noted episodes of transient confusion. The patient has bilateral foot drop and atrophy; mild wrist weakness is also present. Deep tendon reflexes are absent in the lower extremities. His CBC shows an anemia with hemoglobin of 9.6 g/dL; examination of the peripheral blood smear shows basophilic stippling. Which of the following is the most likely cause of this patient's symptoms?

A. Thalassemia
B. Sickle cell disease
C. Pyruvate kinase deficiency
D. Glucose-6-phosphate dehydrogenase deficiency

**Correct Answer:** B. Sickle cell disease

**Core Concept:**

Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the HBB gene, which codes for beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin molecules called hemoglobin S, which cause red blood cells to become rigid and crescent-shaped, leading to hemolysis, reduced oxygen-carrying capacity, and microvascular occlusion.

**Why the Correct Answer is Right:**

The correct answer, Sickle cell disease (option B), is chosen due to the presence of basophilic stippling on peripheral blood smear, which is a characteristic feature of this condition. Basophilic stippling indicates the presence of sickle hemoglobin (HbS) in red blood cells. The other options do not present basophilic stippling:

A. Thalassemia: This is a group of inherited disorders characterized by reduced synthesis of alpha or beta-globin chains. The presence of basophilic stippling is not typically seen in thalassemia unless associated with sickle cell trait.

C. Pyruvate kinase deficiency: This is an enzyme deficiency that leads to impaired glycolysis, causing anemia. Basophilic stippling is not a feature of pyruvate kinase deficiency.

D. Glucose-6-phosphate dehydrogenase deficiency: This is an enzyme deficiency leading to hemolysis due to oxidative stress. Basophilic stippling is not a feature of glucose-6-phosphate dehydrogenase deficiency.

**Why Other Answers are Incorrect:**

A. Thalassemia: While thalassemia can lead to anemia, basophilic stippling is not a common feature.
C. Pyruvate kinase deficiency: This condition is characterized by impaired glycolysis, leading to anemia, but basophilic stippling is not a feature of this condition.
D. Glucose-6-phosphate dehydrogenase deficiency: Hemolysis is a feature of this condition, but basophilic stippling is not typically observed.

**Clinical Pearls:**

1. The presence of basophilic stippling in a peripheral blood smear is a common feature in sickle cell disease (SCD), which is a form of thalassemia. The correct answer is SCD (option B).
2. Basophilic