Fogo, Ch. 7 - Thin membrane disease and Alport syndrome

Question 1

What is the etiology of Alport syndrome?

Answer 1

Usually x-linked recessive loss of COL4A5, but possibly also 4A3/4A4 and rarely autosomal dominant.

Question 2

What are the LM fndings in Alport syndrome?

Answer 2

Nothing early, then sclerosis and fibrosis.

Question 3

What are the IF findings in Alport syndrome?

Answer 3

Nonspecific mesangial IgM. Loss of special immunofluorescence for collagen IV.

Question 4

What are the EM findings for Alport syndrome?

Answer 4

Irregular thick and thin “basket-weaving” look to the GBM. Thickness usually <250nm in adults.

Question 5

What are some clinical concerns in Alport syndrome?

Answer 5

Presents with ESRD, hearing loss, and anterior lenticonus.

Question 6

How does thin basement membrane disease present?

Answer 6

With benign familial hematuria, but some cases can progress to sclerosis and ESRD.

Question 7

What are the LM, IF, and EM findings in thin basement membrane disease?

Answer 7

No LM findings.

No IF findings (usually, may catch some Alport pts).

Diffuse GBM thinning (not just segmental).

Question 8

What causes thin basement membrane disease?

Answer 8

Many different possible inherited factors which can also affect collagen IV as Alport syndrome does.

Question 9

What can be seen in post-renal-transplant Alport patients?

Answer 9

Anti-GBM disease (new exposure to collagen IV).

Question 10

Are children affected in Alport syndrome?

Answer 10

Generally not; children express different alpha trimers in collagen IV.