Alport syndrome

Question 1

Sensorineural hearing loss, hematuria/proteinuria, family history of renal disease, ocular abnormalities, taken together is likely … ?

Answer 1

Alport syndrome

Mutation in COL4A3, COL4A4, or COL4A5 affecting type IV collagen in the GBM, cochlea, and lens.

Question 2

What is the genetic mutation responsible for Alport syndrome?

Answer 2

Mutations in the COL4A3, COL4A4, or COL4A5 genes, which encode type IV collagen.

Question 3

What are the triad of clinical features in Alport syndrome?

Answer 3

Hematuria/proteinuria (renal disease due to GBM damage).
Bilateral sensorineural hearing loss (cochlear damage).
Ocular defects (anterior lenticonus, retinopathy).

Question 4

What is seen on kidney biopsy in Alport syndrome?

Answer 4

GBM splitting and lamellation (“basket-weave” appearance) on electron microscopy.

Question 5

What inheritance pattern is most common in Alport syndrome?

Answer 5

X-linked dominant
(most common form, affecting males more severely).

Autosomal recessive and autosomal dominant forms are less common but also exist.

The other major disease that is X-linked dominant is Fragile X.

Question 6

What type of hearing loss is seen in Alport syndrome?

Answer 6

Bilateral sensorineural hearing loss that usually develops in childhood or adolescence.

Question 7

Which eye abnormality is classically associated with Alport syndrome?

Answer 7

Anterior lenticonus (abnormal conical protrusion of the lens).

Question 8

How does family history help in diagnosing Alport syndrome?

Answer 8

Family history may reveal male relatives with end-stage renal disease (ESRD) or hearing loss at a young age.

Question 9

What treatment is used to slow the progression of kidney disease in Alport syndrome?

Answer 9

ACE inhibitors (like enalapril) to reduce proteinuria and slow progression to ESRD.