A 48-year-old man reports lifelong passage of urine that darkens on standing, progressive spinal stiffness, and knee pain. Examination shows blue-black pigmentation of the ear cartilage and sclerae. Radiographs reveal dense calcification and narrowing of multiple intervertebral discs with vacuum phenomena, but the sacroiliac joints are normal. The underlying enzyme defect is:

• A Alpha-L-iduronidase deficiency
• B Phenylalanine hydroxylase deficiency
• C Cystathionine beta-synthase deficiency
• D Homogentisate oxidase deficiency ✓

Explanation

Alkaptonuria from homogentisate oxidase deficiency causes accumulation of homogentisic acid, which polymerizes and binds collagen, producing the dark urine, ochrontic pigmentation of cartilage, and ochronotic spondyloarthropathy with disc calcification. Its key discriminator from ankylosing spondylitis, given here, is sparing of the sacroiliac joints alongside prominent disc changes. Phenylalanine hydroxylase deficiency is phenylketonuria, cystathionine beta-synthase deficiency is homocystinuria with marfanoid habitus, and alpha-L-iduronidase deficiency causes mucopolysaccharidosis I, none of which produce disc calcification with pigmented cartilage.

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.