A 22-year-old man presents with hematuria, proteinuria (2.5 g/day), and sensorineural hearing loss. His maternal uncle died of renal failure. Electron microscopy of his renal biopsy shows irregular thinning and thickening of the GBM with a characteristic 'basket-weave' or 'moth-eaten' pattern of lamellation. The diagnosis is:

• A Thin basement membrane nephropathy (benign familial hematuria)
• B IgA nephropathy
• C Hereditary focal segmental glomerulosclerosis (NPHS2/podocin mutation)
• D Alport syndrome ✓

Explanation

Alport syndrome is a hereditary nephritis caused by mutations in genes encoding type IV collagen (COL4A3, COL4A4, or COL4A5 — X-linked most common with COL4A5). The GBM normally contains type IV collagen α3α4α5 heterotrimer; its absence leads to the characteristic EM finding of GBM lamellation — irregular alternating thinning and thickening with a 'basket-weave' or 'moth-eaten' pattern. Clinical triad: hematuria, sensorineural hearing loss, and ocular anomalies (anterior lenticonus). Thin basement membrane nephropathy (COL4A3/A4 heterozygous carrier) shows diffuse, uniform GBM thinning without lamellation.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.