Glucose-6-phosphate dehydrogenase deficiency
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Glucose-6-phosphate dehydrogenase deficiency


Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! Glucose-6-phosphate dehydrogenase deficiency,
or G6PD deficiency, is a genetic disorder characterized by decreased levels of glucose-6-phosphate
dehydrogenase, which leads to the destruction of red blood cells. Normally, as a part of the metabolic process,
our body produces free radicals like hydrogen peroxide, or H2O2. Free radicals can damage the cells in many
ways including destroying the DNA, proteins, and the cell membrane. Now, we have a molecule in our body called
glutathione which acts as an antioxidant and goes around and neutralizes these free radicals. In order to function, these molecules need
to be in the reduced state where they can donate an electron to the H2O2 and convert
them into harmless water and oxygen. However this causes the glutathione to become
oxidized, so before it can get back to work, an enzyme called glutathione reductase will
use an NADPH as an electron donor and and reduce the oxidized glutathione back into
its working state. After giving up its electron, the NADPH will
become NADP+. So to replenish the supply of NADPH, we have
the glucose-6-phosphate dehydrogenase enzyme, or G6PD, which reduces NADP+ back to NADPH
by oxidizing a glucose-6-phosphate. Glucose-6-phosphate is a metabolite of glucose
so we usually have a ready supply of this molecule as long as we are not starving. Now G6PD deficiency is caused by mutations
on the G6PD gene which is found on the X chromosome and thus it’s an X-linked recessive genetic
condition and it almost exclusively manifests as a disease in men, since they have one X
and one Y chromosome, so if the one and only chromosome has the mutation, then they have
the disorder. Women on the other hand have two X chromosomes,
so those with an X chromosome that has the mutation, still have another X chromosome
with a normal copy of the gene and thus females are usually carriers and only transmit the
disease to their sons. The G6PD mutations cause defective G6PD enzymes
to be produced and these have a shorter half-life, meaning they don’t last as long as the normal
enzymes. There are two common types of G6PD deficiency:
a Mediterranean and an African variant. The Mediterranean variant is characterized
by a more markedly reduced half-life of G6PD. Now, sometimes this can actually be an advantage
since it provides protection against falciparum malaria. G6PD deficiency makes the parasite-infected
erythrocyte more susceptible to dying from oxidants, which will also kill the malaria
parasites. So despite the obvious downside to having
any of these diseases, they do offer an upside when it comes to warding off a malaria infection. In fact, because malaria has historically
circulated in Africa, the genes underlying these diseases are thought to have conferred
a natural selection advantage and therefore became more common in the genetic pool. Okay, so low levels of G6PD causes low levels
of NADPH, leading to low levels of reduced glutathione. Now G6PD is the only way for red blood cells
to get NADPH so they are especially susceptible to damage caused by free radicals. When these build up, it causes the cell membrane
to become unstable, causing their lysis, or hemolysis. Free radicals can also directly damage hemoglobin
molecules which are the oxygen carrying protein in red blood cells. These damaged proteins precipitates inside
the cells and are called Heinz bodies. The spleen macrophages, that are responsible
for eating up old or abnormal red blood cells, notice these Heinz bodies and try to remove
them by taking a bite out of the cells, leaving these red blood cells partially devoured,
so we call them bite cells. Now, the good news is that only older red
blood cells are at risk for lysis and the hemolytic episode is self-limited as hemolysis
stops when only younger red blood cells remain. Now, when a red blood cell dies, its hemoglobin
breaks up into globin and heme. Heme is converted into bilirubin which is
then taken up by the liver cells and eventually secreted out with bile. If all of a sudden your body starts breaking
down more red blood cells than the liver cells can handle, the excess bilirubin stays in
the blood and cause jaundice where the bilirubin deposits in the skin and the eyes, causing
them to turn yellow. Some of the bilirubin is converted to urobilin
which is what gives urine that yellow color. If there’s too much of it, the urine becomes
a much darker, tea-like color. This could also overwhelm the kidneys resulting
in kidney damage. Okay, so there’s a long list of things that
could increase free radical production and when there’s too much free radicals for
the body to handle, it’s called oxidative stress, which leads to hemolytic episodes. These include infections like viral hepatitis
or pneumonia, metabolic acidosis, and foods and drinks like fava beans, soy products,
red wine, and others. Also certain medications can act as oxidant
stressors like primaquine and chloroquine, which are ironically used to treat malaria. Other common drugs include painkillers like
aspirin and ibuprofen, quinidine that is used to treat arrhythmias, and other drugs that
contain sulfonamide like the antibiotics trimethoprim. OK. Now most of the patients with G6PD deficiency
are completely asymptomatic until exposed to an oxidative stressor. Symptoms of acute hemolysis include jaundice,
dark tea-colored urine, back pain due to kidney damage and anemic symptoms like fatigue, hypotension,
tachycardia, confusion, and others. The diagnosis can be suspected if there is
a history of recent exposure to an oxidant like starting a new medication or eating a
fava bean pita followed by a hemolytic episode. Blood tests will show findings of hemolytic
anemia like low levels of red blood cells and increased levels of reticulocytes, which
are immature red blood cells made by the bone marrow in an attempt to keep up with the red
blood cell loss. Also, there will be high levels of lactate
dehydrogenase, or LDH, which is an intracellular enzyme released in the blood. Next, there is high bilirubin and low haptoglobin
which is a molecule that binds free hemoglobin in the blood. Also, the Coombs test that is used to detect
immune mediated anemias will be negative. Now the blood smear will show bite cells,
and Heinz bodies that are characteristic of G6PD deficiency and can be visualized with
a special Heinz stain as dark intracellular inclusions within the red blood cells. But the definitive test for G6PD diagnosis
is an enzyme assay to detect the levels of G6PD. Given the high risk of hemolysis, it’s important
to diagnose G6PD deficiency as early as possible and so newborns in many developed countries
are tested a few days after birth. Now because G6PD deficiency is a genetic condition
there is no known cure other than avoiding known triggers. Treatment during an hemolytic episode include
hydration and blood transfusion might be needed depending on the severity of the hemolysis. All right, as a quick recap. G6PD deficiency is an X-linked recessive disorder
and it’s characterized by low levels of glucose-6-phosphate dehydrogenase. In G6PD deficiency, red blood cells are susceptible
to oxidative stress which results in hemolysis. This is usually in response to certain triggers
like infections, foods like fava beans and medications like sulfa-drugs and antimalarials. Symptoms include jaundice, dark urine, back
pain and anemia. Typical findings on the blood smear are Heinz
bodies and bite cells. Diagnosis can be confirmed with an enzyme
assay. The mainstay of treatment is to avoid oxidant
factors, but a transfusion might be needed if the hemolysis is severe.

28 thoughts on “Glucose-6-phosphate dehydrogenase deficiency

  1. FINALLY, I CAN SEND THIS TO MY OTHER FRIENDS AND RELATIVES WHO DON'T UNDERSTAND G6PD.
    I am born with it and always find it hard to explain those who don't have it.

  2. Hello I have a small suggestion can you please create playlists for your videos? It would save us a lot of time❤️

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