Know the clinical presentation and mode of inheritance of Alport’s syndrome

• Most commonly inherited in an X-linked dominant pattern (but can be autosomal recessive or dominant)

• Commonly present with gross or microscopic hematuria – often with RBC casts

• Proteinuria may occur

• Rarely nephrotic syndrome develops

• Symptoms usually appear between 5 and 20 years with renal failure at ~ 20 – 50

• Auditory defects may be subtle

• Various eye disorders, usually of lens and cornea

Know LM, EM, and immunohistochemistry findings in Alport’s syndrome

• LM

• Segmental proliferation or sclerosis (or both)

• Persistence of fetal-like glomeruli

• Presence of foam cells

• Increasing glomerulosclerosis, vascular narrowing, tubular atrophy, and interstitial fibrosis as disease progresses

• EM – characteristic findings

• GBM shows irregular foci of thickening and attenuation

• Pronounced splitting and lamination of lamina densa

• Similar alterations in tubular BM

• Immunochemistry – specific antibodies can determine whether specific α chains are present or absent (see below)

Know the pathogenesis of Alport’s syndrome

• Defective glomerular basement membrane synthesis underlies disease

• In X-linked disease, defective gene encodes the α ₅ chain of collagen type IV

• Patient synthesizes less of other α chains (especially 3 and 4), and therefore does not stain w/ antiGBM antibodies

Know how to differentiate Alport’s syndrome and thin basement membrane disease clinically and pathologically

Category: Pathology Notes