Hereditary Spherocytosis

Question 1

How is this disorder inherited ?

Answer 1

Autosomal dominant

Question 2

What is the cause of hereditary spherocytosis?

Answer 2

Mutations in the genes that code for four different proteins that help make up the cytoskeleton.

1) spectrin
2) Ankyrin
3) band 3
4) protein 4.2

Question 3

What is the common functional role of these proteins that make up the cytoskeleton ?

Answer 3

They facilitate vertical interactions between the cytoskeleton and the lipid bilayer of the plasma membrane.

Question 4

What is the resulting effect of mutations in these proteins ?

Answer 4

1( disruption of the interaction between cytoskeleton and membrane.

2) this is followed by vesculation of the unsupported membrane components leading to progressive reduction in membrane surface area and production of a spherocyte shape red blood cell

Question 5

Why does the ‘spherocyte’ shape become a problem?

Answer 5

The red cell membranes are now less flexible.

Which means they become trapped and damaged as they pass through the capillaries in the spleen which results in a reduction of the red blood cell lifespan .

• the problem is in the spleen rather than small capillaries since the red cells return to nearly normal lifespan following splenectomy.

Question 6

Why do people with hereditary spherocytosis have an enlarged spleen ?

Answer 6

• as the red blood cells move through the capillaries in the spleen they become trapped and damaged.
• this means that the spleen will work harder to try and remove these damaged red blood cells.
• causing it to grow in size.

Question 7

What are symptoms of people with hereditary spherocytosis?

Answer 7

1) splenomegaly
2) jaundice
3) Howell jolly bodies will be seen within red blood cells ( basophilic nuclear fragments remained in the RBC)

Question 8

What are the four main complications can occur in patients with HS ?

Answer 8

1) splenomegaly- more likely to rupture .
2) jaundice ( due to increase breakdown of haemoglobin in RBC which results in a rise in bilirubin)
3) Anaemia because there is an increase destruction of RBC.
4) gall bladder problems - gall stones.

Question 9

Given that spherocyte are smaller than normal red blood cells , why is it the MCV below the lower limit of normal ?

Answer 9

• there is an increase in haemopoiesis because of EPO being released from kidney to try and counteract the lysis of RBC in the spleen.
• this means there is more reticulocytes - which are larger than normal RBC because of their RNA.
• so overall the MCV is still within the limit because the size of the reticulocytes outweighs the size of spherocyte.

Question 10

For those with very symptomatic HS, what is the main surgical management ?

Answer 10

Splenectomy