**Core Concept**
Splenectomy, or the surgical removal of the spleen, is typically considered for conditions where the spleen is enlarged (splenomegaly) or when there is a specific indication for its removal. However, there are instances where splenectomy can be effective in treating a disease without splenomegaly.

**Why the Correct Answer is Right**
In Hereditary Spherocytosis (HS), a genetic disorder affecting the red blood cell membrane, splenectomy can be effective even in the absence of splenomegaly. This is because the spleen in HS is hyperactive and prematurely destroys red blood cells, leading to anemia and other complications. Removing the spleen can alleviate these symptoms and improve quality of life. The pathophysiology of HS involves mutations in genes encoding proteins of the red blood cell membrane, leading to spherocytic red blood cells that are more prone to destruction in the spleen.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because Thalassemia major does not typically require splenectomy without prior splenomegaly. While splenectomy may be considered in some cases of Thalassemia, it is not the primary indication for the procedure.
**Option B:** This option is incorrect because Gaucher's disease, a lysosomal storage disorder, may involve splenomegaly, and splenectomy is often considered in the management of this condition.

**Clinical Pearl / High-Yield Fact**
In Hereditary Spherocytosis, splenectomy is often considered when patients are anemic, have significant jaundice, or have a high reticulocyte count, indicating increased red blood cell turnover.

**Correct Answer: C. Hereditary Spherocytosis**