Enzymopathies- G6PD deficiency & PK deficiency Flashcards
What is the function of the enzyme Glucose-6-phosphate dehydrogenase (G6PD)?
It functions to reduce nicotinamide adenine dinucleotide phosphate (NADP) to NADPH.
What is the purpose of NADPH?
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
What are the types of G6PD Deficiency ?
- 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
Where is Type B G6PD Deficiency most commonly seen?
In the Middle East
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.
TRUE!!
True or False? The female homozygotes of G6PD deficiency have an advantage of resistance to Falciparum malaria.
FALSE!! The female HETEROZYGOTES of G6PD deficiency have an advantage of resistance to Falciparum malaria.
True or False? G6PD Deficiency is MOST severe in the Middle Eastern and South-East Asian people.
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 *
True or False? In G6PD Deficiency the blood count remains normal.
TRUE!!
What are the main Clinical Features of G6PD Deficiency ?
- Acute haemolytic anaemia in response to oxidant stress - in response to drugs, fava beans or infections etc.
- Neonatal jaundice, usually without haemolysis.
- Rarely, a congenital non-spherocytic haemolytic anaemia.
What is the name of the oxidant chemical found in Fava beans?
Divicine
How is G6PD Deficiency diagnosed?
Screening Tests
Direct enzyme assay on red cells
What type of cells are found in G6PD deficiency?
- Contracted and fragmented cells
- Bite cells
- Blister cells
- Heinz bodies
“Stress makes me eat bites of fava beans with Heinz ketchup.”
What are Heinz bodies?
These are oxidized, denatured and insoluble haemoglobin that precipitates in the red cell.
Heinz bodies are normally removed by which organ?
The spleen
What are the agents that may cause haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD) deficiency?
- 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
In patients with G6PD that have neonatal jaundice, what is this caused by?
The jaundice is usually not caused by excess haemolysis, but by deficiency of G6PD affecting neonatal liver function.
What is the treatment for patients with G6PD experiencing neonatal jaundice ?
Phototherapy and Exchange transfusion.
True or False? Pyruvate Kinase deficiency is Autosomal Dominant.
FALSE!! It is Autosomal RECESSIVE.
What is the pathogenesis of PK deficiency ?
The red cells become rigid as a result of reduced adenosine triphosphate (ATP) formation.
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).
TRUE!!
What are the Clinical Features of Pyruvate Kinase Deficiency?
- Jaundice
- Gallstones
- Frontal bossing
- Leg ulcers
- Perinatal complications including hydrops, prematurity, neonatal jaundice and anaemia are common.
What type of cells are found in Pyruvate Kinase deficiency?
Poikilocytosis and distorted ‘prickle’ cells are seen post-splenectomy.
Fill in the blanks. “ ________________ is used to make the diagnosis for Pyruvate Kinase Deficiency .
Direct Enzyme Assay
Which stain is used to show Heinz bodies ?
Supravital staining - also used for reticulocytes.