Enzymopathies- G6PD deficiency & PK deficiency

Question 1

What is the function of the enzyme Glucose-6-phosphate dehydrogenase (G6PD)?

Answer 1

It functions to reduce nicotinamide adenine dinucleotide phosphate (NADP) to NADPH.

Question 2

What is the purpose of NADPH?

Answer 2

NADPH is needed for the production of reduced glutathione in which a deficiency renders the red cell susceptible to oxidant stress.

• Reduced Glutathione (GSH) protects the cells from oxidant stress

Question 3

What are the types of G6PD Deficiency ?

Answer 3

• Type B - designated G6PD-Mediterranean and most commonly seen in the Middle East.
• Type A - designated G6PD-A(-)in Africans, found in about 10% of African-Americans

Question 4

Where is Type B G6PD Deficiency most commonly seen?

Answer 4

In the Middle East

Question 5

True or False? In G6PD Deficiency ,the inheritance is sex-linked, affecting MALES, and carried by females who show approximately half the normal red cell G6PD values.

Answer 5

TRUE!!

Question 7

True or False? The female homozygotes of G6PD deficiency have an advantage of resistance to Falciparum malaria.

Answer 7

FALSE!! The female HETEROZYGOTES of G6PD deficiency have an advantage of resistance to Falciparum malaria.

Question 8

True or False? G6PD Deficiency is MOST severe in the Middle Eastern and South-East Asian people.

Answer 8

FALSE!! It is MOST SEVERE in the Mediterranean people.

Mild - in African Americans
More severe in Middle East and South- East Asian people
Most severe in Mediterranean people.

• Severe deficiency occurs in Northern European people too *

Question 9

True or False? In G6PD Deficiency the blood count remains normal.

Answer 9

TRUE!!

Question 10

What are the main Clinical Features of G6PD Deficiency ?

Answer 10

1. Acute haemolytic anaemia in response to oxidant stress - in response to drugs, fava beans or infections etc.
2. Neonatal jaundice, usually without haemolysis.
3. Rarely, a congenital non-spherocytic haemolytic anaemia.

Question 11

What is the name of the oxidant chemical found in Fava beans?

Answer 11

Divicine

Question 12

How is G6PD Deficiency diagnosed?

Answer 12

Screening Tests
Direct enzyme assay on red cells

Question 13

What type of cells are found in G6PD deficiency?

Answer 13

• Contracted and fragmented cells
• Bite cells
• Blister cells
• Heinz bodies

“Stress makes me eat bites of fava beans with Heinz ketchup.”

Question 14

What are Heinz bodies?

Answer 14

These are oxidized, denatured and insoluble haemoglobin that precipitates in the red cell.

Question 15

Heinz bodies are normally removed by which organ?

Answer 15

The spleen

Question 16

What are the agents that may cause haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Answer 16

• Infections and other acute illnesses (e.g. diabetic ketoacidosis)
• Drugs
  ■ Antimalarials (e.g. primaquine, pamaquine, chloroquine, Fansidar, Maloprim, quinine)
  ■ Sulphonamides and sulphones (e.g. co-trimoxazole, sulfanilamide, dapsone, sufasalazine)
  ■ Other antibacterial agents (e.g. quinolones, nitrofurans, nalidixic acid, chloramphenicol)
  ■ Analgesics (e.g. aspirin); moderate doses are safe
  ■ Antihelminths (e.g. β-naphthol, stibophen)
  ■ Miscellaneous (e.g. vitamin K analogues, rasburicase,
  glibenclamide, naphthalene (mothballs), probenecid)
• Fava beans
• Chemical oxidants

Question 17

In patients with G6PD that have neonatal jaundice, what is this caused by?

Answer 17

The jaundice is usually not caused by excess haemolysis, but by deficiency of G6PD affecting neonatal liver function.

Question 18

What is the treatment for patients with G6PD experiencing neonatal jaundice ?

Answer 18

Phototherapy and Exchange transfusion.

Question 19

True or False? Pyruvate Kinase deficiency is Autosomal Dominant.

Answer 19

FALSE!! It is Autosomal RECESSIVE.

Question 20

What is the pathogenesis of PK deficiency ?

Answer 20

The red cells become rigid as a result of reduced adenosine triphosphate (ATP) formation.

Question 21

True or False? In PK deficiency there is a shift to the RIGHT in the oxygen (O2) dissociation curve caused by a RISE in intracellular 2,3-diphosphoglycerate (2,3-DPG).

Answer 21

TRUE!!

Question 22

What are the Clinical Features of Pyruvate Kinase Deficiency?

Answer 22

• Jaundice
• Gallstones
• Frontal bossing
• Leg ulcers
• Perinatal complications including hydrops, prematurity, neonatal jaundice and anaemia are common.

Question 23

What type of cells are found in Pyruvate Kinase deficiency?

Answer 23

Poikilocytosis and distorted ‘prickle’ cells are seen post-splenectomy.

Question 24

Fill in the blanks. “ ________________ is used to make the diagnosis for Pyruvate Kinase Deficiency .

Answer 24

Direct Enzyme Assay

Question 25

Which stain is used to show Heinz bodies ?

Answer 25

Supravital staining - also used for reticulocytes.