Unit 2 - Abali - Lecture 8 - Glucose 6 Phosphate Dehydrogenase Deficiency Flashcards
What is glucose 6 phosphate dehydrogenase deficiency?
Mutation to G6PD gene
Causes RBCs to become more susceptible to oxidative injury and leads to hemolysis
Causes hemolytic anemia: RBCs are destroyed faster than they are produced
Presence of reduced glutathione
Epidemiology
Present in less than 1% in most regions
Common in mediterranean, jews, African Americans, and Africans
Similar to sickle cell: Offers protection from malaria
Affects boys more! → X linked
Presentation of Illness
Present asymptomatic until they consume something oxidizing
Symptoms
Hemoglobinuria
Yellow skin
Kidney injury
Back pain
G6DP Deficiency mechanism
Our cells produce free radicals
If these free radicals become oxidized, they can cause damage
We have an antioxidant called glutathione to stop this damage: reduced state of glutathione
Reduced state protects cells from oxidative stress from hydrogen peroxide by turning it into water
Too keep glutathione reduced, NADPH needs to be kept as NADP+
Due to the lack of G6PD, NADPH stays in its reduced form
This causes oxidative stress and cell death!
Oxidizing agents (Stressors)
Fava beans
Drugs such as sulfonamides, dapsone, cotrimoxazole, aspirin, primaquine, nitrofurantoin, chloramphenicol, and rasburicase
Parvovirus B19 infection
Pathology
Heinz bodies
occur when free radicals break disulfide bonds and cause the dissociation of hemoglobin into heme and globin
Neutrophils identify heinz bodies and “bite them off” since they are abnormal, causing bite cells
Spherocytes
When bite cells become more round
after circulating. Extravascular hemolysis destroys them in the spleen
Homozygous Mutation (present on both XX or XY)
high hemolysis and anemia
Heterozygous mutation (only on one of the XX)
Normally asymptomatic unless exposed to
drugs (primaquine, anti-malarial drug) or
compounds (fava beans) that produce ROS
Diagnosis
a low hemoglobin (Hb) and hematocrit (Hct). These are generally normal when a crisis is not occurring.
As in other hemolytic anemias, a liver function panel will show evidence of hemolysis. This means increased indirect (unconjugated) bilirubin, low haptoglobin, and elevated lactate dehydrogenase (LDH).
During a hemolytic crisis the urinalysis may show heme (due to the filtered hemoglobin). The serum creatinine may be elevated due to acute kidney injury from the toxic effect of the filtered hemoglobin on the renal tubular cells.
Do you screen for G6PD deficiency before or after an episode?
Screening for G6DP before a crisis will demonstrate low levels, thus demonstrating a deficiency.
!!!!!!The study should not be done during or immediately after a hemolytic crisis, since the newly made RBCs and reticulocytes have a relatively higher G6PD activity, so will mask the reduced enzyme activity characteristic of the disorder.!!!!!!
Management
Avoid oxidizing agents
Treatment is unnecessary because new RBCs are produced
