A 28-year-old man has progressive night blindness, anosmia, cerebellar ataxia, and ichthyosis. Nerve biopsy shows sural nerve thickening. Plasma contains markedly elevated phytanic acid, a branched-chain fatty acid from dairy products and fish. The defective process is:

• A Peroxisomal beta-oxidation of very long chain fatty acids
• B Alpha-oxidation of branched-chain fatty acids in peroxisomes ✓
• C Mitochondrial medium-chain acyl-CoA dehydrogenase activity
• D Microsomal omega-oxidation of dicarboxylic acids

Explanation

Refsum disease results from deficient phytanoyl-CoA alpha-hydroxylase, blocking peroxisomal alpha-oxidation, the route required for 3-methyl-branched fatty acids such as phytanic acid, whose methyl group prevents normal beta-oxidation until one carbon is removed. VLCFA beta-oxidation defects cause adrenoleukodystrophy or Zellweger spectrum with elevated straight-chain VLCFAs, not phytanate. MCAD deficiency presents with hypoketotic hypoglycemia after fasting, and omega-oxidation is a minor microsomal salvage pathway.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.