A 6-month-old infant with progressive hypotonia, hepatosplenomegaly, and a cherry-red spot on fundoscopy has an enzyme assay showing markedly reduced hexosaminidase A activity. Which lysosomal storage disorder is this, and what is the mode of inheritance?

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

Explanation

Tay-Sachs disease is caused by hexosaminidase A deficiency (HEXA gene mutation), leading to accumulation of GM2 ganglioside in neurons. The classic infantile form presents with hyperekplexia (exaggerated startle), progressive neurodegeneration, hypotonia, and cherry-red macula (caused by ganglioside accumulation in perimacular ganglion cells with a clear fovea appearing red against pale retina). It is autosomal recessive and more prevalent in Ashkenazi Jews. Niemann-Pick disease is due to sphingomyelinase deficiency (also has cherry-red spot) but is distinguished by the specific enzyme assay.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.