A 4-month-old infant with delayed developmental milestones is evaluated. He has a cherry-red spot on fundoscopy, exaggerated startle response to sound (hyperacusis), progressive neurological deterioration, and macrocephaly. Parents are Ashkenazi Jewish. Hexosaminidase A activity is undetectable. Which diagnosis is this and what is the inheritance pattern?

• A Niemann-Pick disease type A — autosomal recessive
• B Gaucher disease type 2 — autosomal recessive
• C GM1 gangliosidosis — autosomal recessive
• D Tay-Sachs disease — autosomal recessive ✓

Explanation

Tay-Sachs disease is caused by autosomal recessive deficiency of hexosaminidase A (HEXA gene mutation), leading to accumulation of GM2 ganglioside in neuronal lysosomes. The cherry-red spot (contrast between lipid-laden pale retinal ganglion cells and normal vascular fovea), exaggerated startle (hyperacusis), progressive neurodegeneration, and macrocephaly in an Ashkenazi Jewish infant are classic. Hexosaminidase A deficiency confirms the diagnosis. Sandhoff disease (total Hex A+B deficiency) is clinically identical but not population-specific. Niemann-Pick type A also causes cherry-red spot but has hepatosplenomegaly and sphingomyelinase deficiency.

Reference: Ghai Essential Pediatrics, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.