Video summary
G6PD deficiency is a genetic condition affecting the enzyme glucose-6-phosphate dehydrogenase, which is crucial for maintaining red blood cell health by generating NADPH. This reducing power is essential for converting hydrogen peroxide into harmless water through a process involving glutathione reductase and reduced glutathione. When G6PD levels are insufficient, oxidative stress accumulates because the cells cannot neutralize harmful radicals like hydrogen peroxide. This leads to damage of the red blood cell membrane and subsequent hemolysis, particularly when the body is exposed to oxidative triggers such as certain infections, foods like fava beans, or specific medications.
The inheritance pattern of this condition follows an X-linked recessive trait, which results in distinct clinical presentations between males and females. Males are typically more severely affected because they possess only one X chromosome; if that chromosome carries the defective gene, they will manifest the disease. In contrast, heterozygous females undergo random X-chromosome inactivation during development, known as the Lyon hypothesis, leading to a mosaic population of red blood cells where some have normal enzyme activity and others do not. While females are generally less severely affected due to this mosaicism, they can still experience symptoms, and their condition serves as a key example proving the mechanism of random X-inactivation.
Clinically, G6PD deficiency is prevalent in regions endemic for *Plasmodium falciparum* malaria because the genetic trait offers a survival advantage against the parasite. The most severe variants, such as the Mediterranean type, often present with neonatal jaundice within the first few days of life and can trigger acute hemolytic anemia upon exposure to oxidative stressors. Common triggers include drugs like primaquine, dapsone, cotrimoxazole, nitrofurantoin, and even high doses of aspirin or paracetamol. Upon exposure, patients may experience intravascular hemolysis characterized by anemia, dark urine due to hemoglobinuria, abdominal pain, and weakness, with symptoms typically appearing two to three days after the triggering event.
Diagnosis is often precipitated by an episode of hemolysis following drug exposure, leading to the identification of Heinz bodies—precipitated denatured hemoglobin attached to the red blood cell membrane—upon supravital staining. In standard peripheral smears, these damaged cells appear as "bite cells" after macrophages in the spleen remove the precipitated protein and damaged membrane sections. Fortunately, the condition is generally self-limited because the half-life of the abnormal enzyme is short, meaning that younger red blood cells produced later contain normal enzyme levels and are not susceptible to hemolysis. Consequently, no specific treatment is required for the anemia itself once triggers are avoided, though severe cases involving renal failure due to pigment nephropathy may necessitate hemodialysis. Management primarily focuses on educating patients to avoid known oxidative triggers and ensuring physicians screen for G6PD deficiency before prescribing potentially harmful medications.
Read the full video transcript
Hello everyone. In this video, we will
talk about G6PD deficiency.
G6PD is an enzyme which is present in
RBCs and it is
basically leading to formation of NADPH
which is a reducing power in the cell.
See, basically for preventing oxidative
injuries, we want to reduce the
oxidative molecules. So, here you see we
are reducing H2O2 to water.
So, we need some reducing power, right?
So, that is in the terms of NADPH which
is generated. So, in the process NADPH
will get oxidized to NADP. Okay, so
there is another enzyme glutathione
reductase. So, first is like you produce
the reducing power NADPH, then
you generate the reduced glutathione.
So, this you see this is oxidized
glutathione and this NADPH is being used
to produce the reduced glutathione. And
this reduced glutathione in turn reduces
this
hydrogen peroxide to water. Okay?
Ultimately, we want to do reduce the
oxidative radicals, right?
So, if this G6PD enzyme is deficient,
what is going to happen? We will not be
produced we will not be able to produce
NADPH and ultimately reduced glutathione
will not be regenerated. Then H2O2 will
be there and this H2O2 is going to
damage the RBC membrane.
Now, this G6PD deficiency is being
inherited as recessive X-linked trait
that I have told you before.
Now, recessive X-linked trait, what
happens that uh
in males, obviously only one X
chromosome is there. So, if that X
chromosome this uh gene is abnormal,
then males will be affected. So, males
definitely at higher risk.
But in what happens? Two X chromosomes
are there.
Okay? So, all RBCs, the erythroid
precursors which are being produced,
they will be having but during
development, what happens that there is
inactivation, random inactivation of
these X chromosome.
Right?
Now,
sometimes normal X chromosome will get
inactivated, sometimes abnormal X
chromosome will get
inactivated. So, in heterozygous
females, we have two population of the
erythroid precursors where in whom
normal X chromosome may be activated and
another one in abnormal chromosome will
be activated. Okay? So, other one is
inactivated basically. So, we get two
population of RBCs as well. In which we
have RBCs with less G6PD and other RBCs
with more G6PD.
So, what I'm trying to tell you that
females, even heterozygous, they are
also affected. The severity will be less
because not all cells are affected, but
they are also affected. Okay? So, this
random X inactivation, that is Lyon
hypothesis. In fact, this Lyon
hypothesis was proved in this these G6PD
deficient people only. It was studied in
this G6PD deficient people. Again, this
is an MCQ which is asked that G6PD
deficiency manifestation as heterozygous
females that proves Lyon hypothesis that
there is random X chromosome
inactivation. Okay?
Now, G6PD deficiency is common in areas
where there is also common Plasmodium
falciparum infection, where this
Plasmodium falciparum infection is
endemic.
Actually, this G6PD deficiency is
protective against Plasmodium
falciparum. Okay? So, that is why both
are seen in one particular area because
people here with G6PD deficiency survive
against this Plasmodium falciparum.
Okay?
Now, this G6PD deficiency, it has many
variants. Two of this, that is G6PDA and
G6PD Mediterranean, they are more
severe. This Mediterranean one is more
severe and and because more common
clinically significant disease.
And this presents as neonatal jaundice
at day two to day three of birth. Not at
birth. Okay? Not at birth.
At day two to three of birth. Okay?
And
since there is G6PD deficiency, there is
acute hemolytic anemia when challenged
by oxidative agents. For example, if
there are certain drugs, infections. So,
normally the RBCs are surviving, but if
there is exposure to these oxidative
agents, then these RBCs are suddenly
damaged. So, there is acute severe
hemolytic anemia seen
two to three days after exposure to
these oxidative agents. Okay? So,
hemolytic anemia is precipitated by
triggers two to three days following
exposure to these triggers. And these
triggers include infections, certain
foods like broad beans, also known as
fava beans. And this
acute hemolytic anemia which occurs with
G6PD deficiency after exposure to this
broad bean that is known as favism. Then
certain drugs. So, that is very
important that
we should know these drugs which can
precipitate hemolysis in G6PD deficient
people because we when we administer
these drugs, we need to screen for this
G6PD deficiency. Okay? So, what are
these drugs?
Well, antimalarials are there, that is
primaquine. then there is dapsone, then
we have certain antibacterial like
cotrimoxazole, nitrofurantoin,
then uh
even acetylsalicylic acid, paracetamol,
okay? So, there's a possible risk, but
we should always know this list and the
common drugs which can cause hemolytic
anemia in uh the G6PD deficient people,
okay? Now,
even patients of G6PD deficiency once
they are diagnosed.
Because initially the diagnosis may
occur that when they are exposed to
these drugs, there is hemolytic anemia
and there will be features of hemolytic
anemia, okay? So, there is uh
actually marked intravascular hemolysis
and suddenly there will be presence of
hemoglobinemia, hemoglobin will appear
in urine, so dark urine will be there.
So, only after exposure to these drugs
they will be diagnosed. So, these uh
patients are counselled to carry the
list of drugs which may be harmful. And
whenever they are being prescribed any
drug, they should tell the physician
there that yes, they are G6PD deficient.
So, what are the clinical features?
Well, 2 to 3 days following trigger
exposure we get intravascular hemolysis,
so there is anemia, hemoglobinemia,
hemoglobinuria,
malaise, weakness, abdominal and lumbar
pain. So, this is basically what we see
uh the signs of intravascular hemolysis.
But ultimately
uh as the drug is uh stopped, as there
is
uh drug is metabolized as well, there is
uh
limitation of the hemolysis. So, this
episode is self-limited and since
hemolysis is only intermittent when
there is exposure to triggering agents
and it is self-limited, features related
to chronic hemolysis generally are
absent. So, we don't see splenomegaly,
gallstones, etc.
What What the peripheral smear? How will
be the peripheral smear? Well,
because of exposure to oxidative agents,
there is precipitation of denatured
hemoglobin.
So,
if we take a blood sample and stain it
supravitally with methyl violet
crystal violet or stain, then we see we
see this is precipitated hemoglobin
which is attached to the membrane, okay?
And this is known as Heinz bodies.
Now, this uh damages the membranes and
there is intravascular hemolysis because
of this. So, this is the pathophysiology
which I was telling there is
intravascular hemolysis. So, why there
is intravascular hemolysis? Because the
membrane damage is there, precipitation
of denatured hemoglobin is there, and uh
there is intravascular hemolysis, okay?
Now,
these Heinz bodies, as they cross
through the spleen, they are also the
macrophages actually remove this part.
So, damaged membrane and the
precipitated hemoglobin it is removed
from the RBCs. So, if we make a
peripheral smear of these, so we also
see these cells in which we see that
some part of the membrane has been
removed. And these cells are known as
bite cells.
Okay? So, in G6PD deficiency, we see
Heinz bodies when we stain the blood
sample with the supravital staining and
make a smear out of it, so Heinz bodies
are seen. And if we stain with normal
smear to make a peripheral smear, we see
bite cells because of
uh removal of those uh precipitated
hemoglobin, membrane damaged membrane by
macrophages, okay?
Now,
no treatment is recommended for this
because the episode is self-limited.
So, only older cells with deficient G6PD
are susceptible to hemolysis.
Yes, half life of G6PD variants, the
abnormal G6PD is there. I told you that
normally also the enzyme the proteins
are getting degraded, but it happens
over a longer time, right? But in these
patients
the half life of protein is lesser,
right? So, half life of G6PD variants is
reduced. So, deficiency does appear in
older cells, but it does appear. So,
whenever the hemolysis is occurring,
younger cells are not damaged in G6PD
because in that there may be normal G6PD
enzyme as well. So, younger cells are
not damaged. With time there is decrease
in G6PD and there is older cells which
are damaged, okay?
However, since there is acute
intravascular hemolysis and that
hemoglobin free hemoglobin which appears
in blood, it filters through the
nephron, okay?
And then it is captured by our tubular
cells. Ultimately, it can lead to
pigment nephropathy and the the cells
which are trapping the hemoglobin will
be released into the tubular fluid and
may may block the nephrons as well. So,
this can lead to renal failure. So, if
that is the manifestation, then
hemodialysis is recommended, okay? And
obviously, we have to counsel the
patient and we have to be careful with
the triggers. Whenever we are
administering these drugs, we have to
take a history, we have to go for G6PD
assessment, okay?
So, that was about G6PD deficiency. I
hope you understood the concept and if
you like the way I explained the
concept, then I think you should
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