inherited HA: enzyme abnormalities Flashcards
2 examples of enzyme abnormalities
1) G6PD defecient
2) PK defecient
how is G6pD inherited
X-linked recessive –> affects only men or rarely females with X-chromosome
(the normal phenomenon in which one of the two X chromosomes in every cell of a female individual is inactivated during embryonic development)
(females may be carriers and pass on to their sons)
G6PD enzyme (glucose 6 phosphate dehydrogenase) is important for what
NADPH production which is
necessary to maintain reduced state glutathione -> protection from oxidative stress ( glutathione protects Hb oxidation)
what is the result of G6PD defecient
no NADPH->decrease glutathione-> increased oxidative stress-> RBCs lysis (intravascular hemolysis )
what are triggers of G6PD
- Infection (most common precipitator)
- Acidosis
- Fava beans
- Drugs: antimalarials, quinine, sulphonamides, quinolones, nitrofurantoin,dapsone, ciprofloxacin
features of G6PD
- Most patients are asymptomatic; dark urine (due to hemoglobinuria bcz of hemolysis ) and jaundice when exposed to triggers
- Normal sized spleen (no organomegaly bcz it’s intravascular hemolysis)
(note: dark urine= intravascular hemolysis, organomegaly =extravascular hemolysis)
- May present as neonatal jaundice (kernicterus: type of brain damage that can result from high
levels of bilirubin in a baby’s blood) , neurological damage
what would blood film of G6PD show
Bite cells
Heinz bodies
helmet basket cells
ghost cells
what is a diagnostic tool of G6pd
G6PD level measurement :
I. G6PD levels may be normal during the hemolytic episode because the RBCs that are most deficient in G6PD have already been destroyed
II. Repeating the test at a later date facilitates diagnosis ( before a new episode > we will find decreased G6PD enzyme in RBCs)
what is a key enzyme in the last step of glycolysis responsible for ATP energy generation
pyruvate kinase
what type of anemia is pyruvate kinase
Inherited extravascular hemolytic anemia
what is diagnosis of PKD
↓ Pyruvate kinase enzyme activity and PKLR gene mutation
what is the reason of hemolysis in PKD
Absence of pyruvate kinase → ATP deficiency in RBC > rigid RBCs → extravascular hemolysis
