Renal biopsy from a 16-year-old boy with hematuria and hearing loss shows splitting of the glomerular basement membrane. Immunofluorescence staining for type IV collagen chains shows complete absence of the alpha-5 chain in the glomerular basement membrane. Which statement best fits this patient?

• A Autosomal recessive inheritance with normal hearing expected
• B X-linked inheritance due to a COL4A5 mutation, with progression to end-stage renal disease ✓
• C Heterozygous COL4A3 mutation causing benign familial hematuria
• D Anti-GBM disease with risk of pulmonary hemorrhage during follow-up

Explanation

Classic Alport syndrome is X-linked, caused by mutations in the COL4A5 gene encoding the alpha-5 chain of type IV collagen. Absent alpha-5 staining in the GBM confirms this defect and predicts progressive renal failure with sensorineural deafness and ocular lesions such as anterior lenticonus. Benign familial hematuria involves heterozygous COL4A3 or COL4A4 mutations with a thin GBM and no deafness. Anti-GBM disease shows linear IgG deposition, not loss of collagen chain staining.

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.