A 28-year-old man reports progressive night blindness, loss of smell, gait unsteadiness, and distal numbness. Examination shows retinitis pigmentosa, cerebellar signs, and absent ankle jerks. Plasma studies reveal markedly elevated levels of a branched-chain fatty acid derived from chlorophyll metabolism. The underlying defect involves which pathway?
- A Alpha-oxidation of phytanic acid due to phytanoyl-CoA hydroxylase deficiency ✓
- B Beta-oxidation of very long chain fatty acids in peroxisomes
- C Omega-oxidation of medium chain fatty acids in microsomes
- D Defective carnitine transport across the mitochondrial membrane
Correct answer: A. Alpha-oxidation of phytanic acid due to phytanoyl-CoA hydroxylase deficiency
Explanation
This is adult Refsum disease. Phytanic acid, a branched-chain fatty acid from dietary chlorophyll derivatives, carries a methyl group on its beta carbon that blocks standard beta-oxidation, so peroxisomal alpha-oxidation removes one carbon first. Defects in phytanoyl-CoA hydroxylase cause accumulation, producing retinitis pigmentosa, anosmia, polyneuropathy, and cerebellar ataxia. Zellweger-type defects kill option B because peroxisome biogenesis causes different findings.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.