Which of the following statements is true of hereditary spherocytosis –
**Core Concept**
Hereditary spherocytosis (HS) is a genetic disorder characterized by the production of abnormal red blood cells (RBCs) that are sphere-shaped instead of the normal biconcave disk shape. This anomaly results in increased RBC membrane surface area to volume ratio, leading to premature destruction in the spleen.
**Why the Correct Answer is Right**
The correct answer is related to the molecular basis of hereditary spherocytosis. The disorder is caused by mutations in genes encoding proteins involved in the formation and maintenance of the RBC membrane skeleton. Specifically, mutations in the **SPTB** gene, which encodes spectrin, and the **ANK1** gene, which encodes ankyrin, are common causes of HS. These mutations lead to the production of abnormal spectrin and ankyrin proteins, which disrupt the RBC membrane skeleton and result in the characteristic spherocytic shape of the RBCs.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because while anemia is a common feature of hereditary spherocytosis, it is not a defining characteristic of the disorder. Anemia occurs as a result of the premature destruction of RBCs in the spleen, but it is not a specific diagnostic criterion.
**Option B:** This option is incorrect because while the spleen is indeed involved in the pathophysiology of hereditary spherocytosis, it is not the primary site of RBC destruction. The spleen acts as a filter, removing abnormal RBCs from the circulation, but the actual destruction occurs in the liver and spleen macrophages.
**Option C:** This option is incorrect because while jaundice is a common feature of hereditary spherocytosis, it is not a specific diagnostic criterion. Jaundice occurs as a result of the increased breakdown of RBCs and subsequent release of bilirubin into the bloodstream.
**Clinical Pearl / High-Yield Fact**
Hereditary spherocytosis is an autosomal dominant disorder, meaning that a single copy of the mutated gene is sufficient to cause the disease. However, the severity of the disorder can vary widely between individuals, even within the same family.
**Correct Answer:** C.