A 3-year-old boy presents with progressive hepatosplenomegaly, developmental delay, and cherry-red spot on the macula. Enzyme assay shows deficiency of hexosaminidase A. Which clinical feature best distinguishes this condition from Gaucher disease?

Explanation

## Distinguishing Tay-Sachs Disease from Gaucher Disease ### Clinical Presentation Comparison | Feature | Tay-Sachs (Hex-A deficiency) | Gaucher Disease (β-glucosidase deficiency) | |---------|-----|-----| | **Cherry-red spot** | Present (pathognomonic) | Absent | | **Primary organ involvement** | CNS (neurological) | Reticuloendothelial (hepatosplenomegaly) | | **Bone disease** | Rare/absent | Common (pathological fractures, Erlenmeyer flask femur) | | **Neurological progression** | Rapid, severe | Absent (except Type 3) | | **Acid phosphatase** | Normal/mildly elevated | Markedly elevated | | **Age of onset** | Infancy (3–6 months) | Variable (Type 1: childhood to adulthood) | ### Key Point: **The cherry-red spot is the hallmark finding that distinguishes Tay-Sachs from Gaucher disease.** It results from accumulation of GM~2~ ganglioside in retinal neurons, creating a pale fovea surrounded by red retina. ### High-Yield: Tay-Sachs = **CNS-dominant** lysosomal storage disorder with macular cherry-red spot. Gaucher disease = **Visceral-dominant** with bone involvement and markedly elevated acid phosphatase. ### Clinical Pearl: The cherry-red spot appears in Tay-Sachs and Sialidosis but NOT in Gaucher disease—this single ophthalmologic finding can differentiate them at the bedside. ### Mnemonic: **TAYS** = Tay-Sachs: **A**cute neurological decline, **Y**ellow (pale) macula with **S**pot, **S**phingolipidosis (GM~2~ ganglioside).