A 7-year-old boy develops progressive spastic paraplegia, skin hyperpigmentation, and adrenal insufficiency. MRI shows symmetric white matter demyelination. Plasma analysis reveals marked elevation of C26:0 hexacosanoic acid. Genetic testing identifies a mutation affecting:

• A Medium-chain acyl-CoA dehydrogenase in mitochondria
• B Microsomal triglyceride transfer protein in intestinal enterocytes
• C The ABCD1 transporter that imports very long chain fatty acyl-CoA into peroxisomes ✓
• D Sterol carrier protein-2 involved in cholesterol esterification

Explanation

X-linked adrenoleukodystrophy arises from mutations in ABCD1, an ATP-binding cassette transporter on the peroxisomal membrane that imports very long chain fatty acyl-CoA for beta-oxidation. Accumulated A24 to A28 saturated fatty acids damage CNS myelin and adrenal cortex, explaining the combined neurologic and endocrine picture. Abetalipoproteinemia (option B) causes acanthocytes and steatorrhea, not adrenal failure or demyelination.

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.