Alport Syndrome Flashcards
A 12-year-old boy presents with a history of recurrent hematuria since childhood. He also reports progressive hearing loss. His family history is significant for end-stage renal disease in his maternal uncle. Examination reveals normal blood pressure and no edema. Laboratory studies show proteinuria and microscopic hematuria. Kidney biopsy demonstrates irregular thinning and thickening of the glomerular basement membrane with a “basket-weave” appearance on electron microscopy. Which of the following is the most likely diagnosis?
A) IgA nephropathy
B) Goodpasture syndrome
C) Alport syndrome
D) Minimal change disease
E) Membranous nephropathy
Answer: Alport syndrome
Explanation: Alport syndrome is a hereditary nephropathy caused by mutations in type IV collagen genes (most commonly COL4A5 in X-linked inheritance). It presents with recurrent hematuria, progressive proteinuria, hypertension, and chronic kidney disease. Sensorineural hearing loss and ocular abnormalities are common extra-renal features. The “basket-weave” appearance of the glomerular basement membrane on electron microscopy is pathognomonic.
Incorrect Answers:
A) IgA nephropathy presents with episodic hematuria, typically following an upper respiratory tract infection, but does not cause hearing loss or GBM abnormalities.
B) Goodpasture syndrome involves hemoptysis, linear IgG deposits, and is not hereditary.
D) Minimal change disease presents with nephrotic syndrome and normal biopsy findings under electron microscopy.
E) Membranous nephropathy is associated with nephrotic syndrome and subepithelial immune complex deposits, not GBM thinning.
What is the genetic basis of Alport syndrome?
Mutations in type IV collagen genes (most commonly COL4A5 in X-linked Alport syndrome)
What is the pathophysiology of Alport syndrome?
Defective type IV collagen disrupts the integrity of the glomerular basement membrane, leading to progressive kidney damage
What are the hallmark clinical features of Alport syndrome?
Hematuria, progressive proteinuria, hypertension, and eventual chronic kidney disease (CKD)
What type of inheritance is most common in Alport syndrome?
X-linked inheritance (85% of cases), but autosomal recessive and dominant forms also exist
What is the characteristic finding on kidney biopsy in Alport syndrome?
Irregular thinning and thickening of the glomerular basement membrane with a ‘basket-weave’ appearance on electron microscopy
What extra-renal manifestations are associated with Alport syndrome?
Sensorineural hearing loss and ocular abnormalities (e.g., anterior lenticonus, retinal flecks)
What are the diagnostic methods for Alport syndrome?
Family history, urinalysis, kidney biopsy, and genetic testing
What is the treatment approach for Alport syndrome?
Management of hypertension (ACE inhibitors or ARBs), treatment of CKD, and renal transplantation in advanced stages
