Alport Workshop

Question 1

What are basement membrance

Answer 1

Thin sheets of extracellular matrix that underlie all epithelial and endothelial cells and surround fat, muscle and Schwann cells. In some tissues like the brain capillaries,
kidney glomerulus, and lung alveoli, the basement membrane (BM) functions as a
highly selective filter.

Question 2

What are the two layers of the basement membrane

Answer 2

Lamina densa and lamina lucida

Question 3

Explain type 4 collagen

Answer 3

It has 6 isoforms of alpha chaing and the triple helix of alpha chains is made by a combination of these.

Question 4

Explain varying BM of type 4 throughout body

Answer 4

1, 1, 2 are in all BM
3,4,5 are in GBM
5,5,6 are in skin and smooth mucles

Question 5

What is alport syndrome

Answer 5

a hereditary disease of the glomerular basement membrane (GBM)
characterized by the familial occurrence of progressive, hematuric nephropathy with
sensorineural deafness.

Question 6

Genetic features of Alport

Answer 6

It’s genentically heterogensous and from a mutation in IV isoform 3,4,5 which make podocytes in GBM

Inheritance pattern-
4Alpha5- Xlinked- hence hwy males get it more– women may get blood in urine from col4alpha 5 but not renal failure like men

Autosomal recessive- 4a3 and 4a4 inherited when both are mutated parents are often carriers with no symtoms – can be due to one missing nucleotide, frame shift, deletion insertion

Question 7

Forautosomal Alport what genes and what end would make it worse

Answer 7

3a4 and 4a4

Since alpha chains are at the C-terminal it would be worst to be near the C-termineal .

Question 8

When is diagnosis of alport not diffucult

Whe is it difficult

Answer 8

Not difficult when they have family history and clinical symptoms are present

more difficult when there is a de novo mutation in 4a5 without family history. They may have hematuria, deafness and ocular abnormalities. you can take a skin biopsy since skin is (556) and if they lack 5 in the skin then they have– X-linked–Alport– if they are on skin then you need a renal biposy to consider if either the 3 or 4 are defective.

Question 9

Therapy of Alport

Answer 9

Usually the affected males and homozygous females develop end-stage renal
disease (ESRD) before the fifth decade of life, while heterozygous females rarely
develop renal failure.

1, ACE inhibitors to reduce protein in urine.

2. Consider drugs that reduce intraglomerular space
3. kidney transport usually successful with 4a5 but ppl with 345 problems more likely to develop GBM nephritis