**Core Concept**
Tay-Sachs disease is a rare autosomal recessive lysosomal storage disorder characterized by the deficiency of hexosaminidase A, leading to accumulation of gangliosides (especially GM2) in neurons. This accumulation causes progressive neurodegeneration, particularly in the central nervous system.

**Why the Correct Answer is Right**
In Tay-Sachs disease, hexosaminidase A deficiency results in the buildup of GM2 gangliosides within neuronal lysosomes. This leads to neuronal swelling, progressive motor and cognitive decline, blindness, and early death—typically by age 4–5 years. The presence of swollen neurons with lipid-filled lysosomes at autopsy is classic for this condition. The disease is inherited in an autosomal recessive pattern and is most common in Ashkenazi Jewish populations.

**Why Each Wrong Option is Incorrect**
Option A: AL amyloidosis involves deposition of amyloid fibrils in tissues, not lysosomal lipid accumulation; it does not cause GM2 ganglioside buildup or early-onset blindness.
Option B: Hurler syndrome (mucopolysaccharidosis I) involves accumulation of glycosaminoglycans due to alpha-L-iduronidase deficiency, leading to skeletal deformities and coarse facial features, not lipid-filled lysosomes or blindness.
Option C: Phenylketonuria results from phenylalanine hydroxylase deficiency, causing phenylketonuria and intellectual disability, but does not involve lysosomal lipid accumulation or blindness.

**Clinical Pearl / High-Yield Fact**
Tay-Sachs disease presents with early-onset neurodegeneration, blindness, and death before age 5. The hallmark is GM2 ganglioside accumulation in neurons—remember this with the mnemonic: **"Tay-Sachs = Tangled GM2, Tearing Neurons."**

✓ Correct Answer: D. Tay-Sachs disease