A 14-year-old boy develops progressive night blindness, loss of smell, cerebellar ataxia, and scaly skin thickening. Plasma analysis shows marked elevation of phytanic acid, a branched-chain fatty acid derived from chlorophyll in the diet. The defective enzyme is:
- A Phytanoyl-CoA hydroxylase ✓
- B Very long chain acyl-CoA dehydrogenase
- C Microsomal triglyceride transfer protein
- D Medium-chain acyl-CoA dehydrogenase
Explanation
Refsum disease results from deficient phytanoyl-CoA hydroxylase, a peroxisomal enzyme performing alpha-oxidation, the only route for degrading the 3-methyl branch of phytanic acid that blocks normal beta-oxidation. Classic tetrad: retinitis pigmentosa, anosmia, ataxia, and polyneuropathy, often with ichthyosis. Unlike Zellweger syndrome, peroxisomes themselves are structurally intact and VLCFA levels are normal, which distinguishes it biochemically. MTP deficiency causes abetalipoproteinemia, and MCAD deficiency causes hypoketotic hypoglycemia in infancy rather than phytanic acid accumulation.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.