An 18-year-old man has persistent microscopic haematuria found on screening. His mother has long-standing haematuria, and a maternal uncle died of renal failure at age 35. Audiometry confirms bilateral sensorineural hearing loss. Light microscopy of his biopsy is non-specific, but electron microscopy shows irregular thickening and thinning of the glomerular basement membrane with splitting and lamellation of the lamina densa. What is the underlying defect?

• A Mutation of the gene encoding podocin leading to foot process effacement
• B Autoantibodies against the NC1 domain of the alpha-3 chain of type IV collagen
• C Mutation of the gene encoding nephrin at the slit diaphragm
• D Mutation of the COL4A5 gene encoding the alpha-5 chain of type IV collagen ✓

Explanation

Alport syndrome results from defective type IV collagen in the glomerular basement membrane. About 85 percent of cases are X-linked due to mutations in COL4D5, matching the pedigree of transmission through affected mothers. The triad of hereditary nephritis, sensorineural deafness, and ocular lesions such as anterior lenticonus, together with basket-weave splitting of the lamina densa on electron microscopy, is characteristic. Anti-GBM antibodies define Goodpasture syndrome, and nephrin or podocin defects cause congenital nephrotic syndrome, not hereditary haematuria.

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.