Hereditary glomerular disease: Alport, thin GBM, Fabry
- Lesion
Faulty collagen IV makes the glomerular basement membrane split, causing hematuria, deafness and eye lesions; Fabry disease stores lipid in podocytes.
What it is
The glomerular basement membrane is built from a network of type IV collagen α3, α4 and α5 chains. Variants in COL4A5 (X-linked) or COL4A3 and COL4A4 (autosomal) produce a spectrum from thin basement membrane with benign hematuria to Alport syndrome, with progressive nephritis, sensorineural hearing loss and eye defects. The same chains are present in the cochlea and lens. Fabry disease is an X-linked lack of α-galactosidase A that fills podocytes and vessels with glycosphingolipid.
Structure
- Alport: glomeruli first look normal; later segmental sclerosis, interstitial fibrosis and foam cells among tubules.
- Immunostaining for collagen IV α5 can show its absence in the GBM (and in skin in the X-linked form).
- Thin basement membrane: uniformly thin GBM with otherwise normal glomeruli.
- Fabry: podocytes swollen and vacuolated on LM; concentric lamellar inclusions on EM.
Hereditary glomerular diseases
| Disease | Defect | Key findings |
|---|---|---|
| Alport syndrome | COL4A5 (X-linked) or COL4A3/COL4A4 | Hematuria, progressive kidney failure, deafness, eye lesions; split, laminated GBM |
| Thin basement membrane | One faulty COL4A3 or COL4A4 copy (carrier state) | Persistent microscopic hematuria, usually benign; uniformly thin GBM |
| Fabry disease | GLA (α-galactosidase A), X-linked | Proteinuria, zebra bodies in podocytes, angiokeratomas, neuropathic pain |
Clinical notes
- Family history of hematuria, kidney failure and hearing aids points to Alport syndrome.
- Fabry disease can be treated with enzyme replacement, so recognizing it matters.
Test yourself
Think of the answer, then tap the question to see it.
Which gene is altered in X-linked Alport syndrome?
COL4A5, which encodes the α5 chain of type IV collagen.
What does EM show in Alport syndrome?
Irregular thinning and thickening of the GBM with splitting and lamination of the lamina densa.
What are zebra bodies and where are they seen?
Lamellated lipid inclusions in podocytes and other cells in Fabry disease, seen by electron microscopy.
Elsewhere in DurgiPedia
- Collagen
- Glomerulus and the filtration barrier: podocytes, mesangium, JGA
- Mendelian inheritance: autosomal dominant, recessive and X-linked
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Alport syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Fabry disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.