A 3-year-old boy who walked normally at 14 months now has progressive gait difficulty, weakness of the lower limbs, absent ankle jerks, and extensor plantar responses. Nerve conduction studies show markedly reduced conduction velocities. MRI brain shows symmetric periventricular white matter changes. Which enzyme deficiency is most likely?

• A Galactocerebrosidase
• B Beta-hexosaminidase A
• C Arylsulfatase A ✓
• D Acid sphingomyelinase

Explanation

Metachromatic leukodystrophy results from arylsulfatase A deficiency causing sulfatide accumulation in central and peripheral myelin. The combination of central demyelination (regression, pyramidal signs, white matter change on MRI) with a prominent peripheral neuropathy (absent reflexes, slow conduction velocities) is its signature, and metachromatic granules appear in urine sediment stained with cresyl violet. Galactocerebrosidase deficiency causes Krabbe disease, where peripheral neuropathy occurs but globoid cells are seen and reflexes may be brisk early.

Reference: Nelson Textbook of Pediatrics, 22nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.