Alport syndrome
Summary
Alport syndrome is an X-linked hereditary nephritis caused by mutations in genes encoding type IV collagen (COL4A5), leading to progressive glomerulonephritis, sensorineural hearing loss, and ocular abnormalities. It primarily affects males and is a leading cause of hereditary kidney disease.
Detail
Alport syndrome results from mutations in genes encoding α-chains of type IV collagen (COL4A3, COL4A4, COL4A5), with 85% of cases being X-linked (COL4A5 mutation). Type IV collagen is crucial for basement membrane integrity in the kidney, ear, and eye. The defective collagen leads to progressive glomerulonephritis with characteristic 'basket-weave' appearance on electron microscopy of the glomerular basement membrane (GBM). Clinical presentation includes hematuria (often the first sign), proteinuria, progressive chronic kidney disease leading to end-stage renal disease (typically by age 30 in males), bilateral sensorineural hearing loss (high-frequency initially), and ocular abnormalities including anterior lens capsule defects and retinal flecks. Males are more severely affected due to X-linked inheritance, while heterozygous females may have milder disease. Diagnosis is confirmed by kidney biopsy showing GBM abnormalities, genetic testing, and family history. Treatment is supportive with ACE inhibitors or ARBs to slow progression, management of CKD complications, and eventual renal replacement therapy.
Sources
- Robbins & Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- Brenner & Rector's The Kidney
- Nelson Textbook of Pediatrics
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