A 12-year-old boy presents with progressive night blindness, anosmia, cerebellar ataxia, and ichthyosis. Serum analysis shows markedly elevated phytanic acid levels. Beta-oxidation of this branched-chain fatty acid is blocked because its 3-methyl group prevents formation of the normal dehydrogenation intermediate. Which pathway must act on phytanic acid before beta-oxidation can proceed?
- A Omega-oxidation in the endoplasmic reticulum
- B Alpha-oxidation with hydroxylation at carbon 3 ✓
- C Peroxisomal thiolase cleavage
- D Carnitine-dependent mitochondrial import
Correct answer: B. Alpha-oxidation with hydroxylation at carbon 3
Explanation
Refsum disease results from defective phytanoyl-CoA alpha-hydroxylase. Phytanic acid carries a methyl group on carbon 3, which blocks the acyl-CoA dehydrogenase step of beta-oxidation. Alpha-oxidation removes one carbon as formyl-CoA after hydroxylation at carbon 3, converting phytanic acid to pristanic acid, which can then undergo peroxisomal beta-oxidation. Omega-oxidation is a minor salvage pathway and does not remove the blocking methyl group, killing option A.
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.