Inherited and Congenital Kidney Disease
Core concepts
Know Alport syndrome (X-linked COL4A5; hematuria, hearing loss, ocular lesions, progressive CKD), thin basement membrane disease (benign familial hematuria), Fabry disease (alpha-galactosidase A; proteinuria, angiokeratomas, neuropathy), cystinosis, primary hyperoxaluria, and congenital anomalies of the kidney and urinary tract (CAKUT). Also autosomal dominant tubulointerstitial kidney disease and nail-patella syndrome.
Genetics: X-linked, autosomal dominant, autosomal recessive, and mitochondrial patterns. Diagnosis: family history, biopsy (electron microscopy for Alport-basket-weave GBM), genetic testing, and enzyme assays.
Traps
Alport can present as isolated hematuria-do not dismiss in a child with hearing loss. Thin basement membrane disease usually has normal renal function. Fabry requires enzyme replacement; proteinuria responds to ACE inhibitors. Hyperoxaluria can cause early stones and graft loss after transplant.
Rule of thumb
Familial hematuria + hearing loss + progressive CKD = Alport; confirm with genetics or EM.
Worked example
A 12-year-old boy with hematuria, sensorineural hearing loss, and a maternal uncle on dialysis: suspect X-linked Alport syndrome; genetic testing and ACE inhibitor for proteinuria.