Wednesday, June 24, 2009

Collagen IV Mutation

A 30 year old woman was recently diagnosed by her family physician with a urinary tract infection. The urinalysis at the time showed microscopic hematuria. At the following visit 3 months later, another urinalysis showed microscopic hematuria with no other abnormalities. Urinary protein excretion and blood pressures are normal. The patient is asymptomatic; she has never seen blood in her urine. She notes that several family members have positive tests for microscopic hematuria but no symptoms and no renal failure. Renal biopsy here is not indicated, but if you did a renal biopsy, you would see the following:

The top is normal; the bottom would be the patient's EM. Light microscopy is normal.

Challenge: Diagnosis?

Image shown under fair use.


Stephanie said...

alport's, abnormally thin basement membrane. associated with deafness too, but male predominance.

tree said...

Alport syndrome

Craig Chen said...

Interesting - I was not going for Alport's; instead, I was thinking basement membrane nephropathy.

You are right in that Alport's is a collagen IV mutation, but if (or when) I write a case on Alport's, it'd most likely be a boy with end stage renal disease, deafness, positive family history, and ocular abnormalities (all the things that Stephanie mentioned). Alport's can present with asymptomatic microscopic hematuria; UpToDate says:
"Other glomerular disorders that present in children with microscopic hematuria include IgA nephropathy, in which the family history is usually negative; and thin basement membrane nephropathy, in which the family history may be positive for hematuria but renal failure and deafness are absent."
Collagen IV Mutation

Thin basement membrane nephropathy (also called benign familial hematuria) is a familial disorder associated in some cases with mutations in collagen type IV. The characteristic manifestation is persistent or intermittent asymptomatic microscopic hematuria incidentally discovered. Renal biopsy shows diffuse thinning of the glomerular basement membrane (150-225nM vs. 300-400nM in a normal kidney). The differential includes IgA nephropathy (gross hematuria with negative family history) and Alport's syndrome (hereditary nephritis, gross hematuria, family history of renal failure, X-linked).

Sources: UpToDate;

Craig Chen said...

Oh - also, the histopath for Alport's is splitting of the glomerular basement membrane and the EM (obviously) shows thinning of the GBM.

You get partial credit though :)

Alex said...

thought alport's, but didn't guess it cuz you did it already: