GLUCOSE -6- PHOSPHATE

DEHYDROGENASE DEFICIENCY
Members
LLANES, Theresa Dianne *

LOCANDO, Edmarie *
LLEMOS, John Zandro *
LLANES, Christian Darwin
LISING, Jeru
LIMPALAN, Melanie

GLUCOSE-6PHOSPHATE
DEHYDROGENASE
DEFICIENCY

a hereditary disease
characterized by abnormally
low levels of glucose-6phosphate dehydrogenase
causing hemolytic anemia due
to inability to detoxify oxidizing
agents

WHAT IS GLUCOSE-6-PHOSPHATE
DEHYDROGENASE?
It is an enzyme in the pentose
phosphate pathway.
It converts glucose-6-phosphate
into 6-phosphoglucono--lactone
It is the rate-limiting enzyme of
this metabolic pathway.

PENTOSE PHOSPHATE PATHWAY

(HMP SHUNT)
a process that generates NADPH and
PENTOSES.
an alternative to glycolysis
takes place in the cytosol
two distinct PHASES : an oxidative phase, in
which NADPH is generated, and a nonoxidative phase involving synthesis of 5carbon sugars.

G6PD/NADPH PATHWAY IN RED

BLOOD CELLS (ERYTHROCYTES)
The G6PD/NADPH pathway via HMP shunt is the only
source of reduced glutathione in red blood cells.
HMP shunt supplies reducing energy by maintaining the
level of the co-enzyme nicotinamide adenine
dinucleotide phosphate(NADPH). NADPH prevents
oxidative stress by reducing glutathione via glutathione
reductase, which converts reactive H2O2 into H2O by
glutathione peroxidase.
Any defect in the production of NADPH could have
profound effects on erythrocyte survival.

FIVE CLASSES OF G6PD

EPIDEMIOLOGY
most common human enzyme
defect, affecting more than 400M
people worldwide
highest prevelance in tropical
Africa, Middle East, South Asia
and parts of the Mediterranean

CLASSIFICATION
I-Very Severe deficiency (<2% activity) with chronic
(nonspherocytic) hemolytic anemia

II-Severe deficiency (<10% activity), with intermittent

hemolysis

III-Mild deficiency (10-60% activity), hemolysis with

stressors only

IV-Non-deficient variant, no clinical consequence

V-Increased enzyme activity, no clinical consequence

Classes

Enzyme deficiency

Hemolysis

Class I

Severe (less than 2%

of normal activity)

Chronic hemolytic
anemia even in the
absence of stress

Class II

Severe (<10% of
normal activity)

Stress required for

hemolysis to be
precipitated

Class III

Moderate (10-60% of Intermittent hemolysis

asssociated with
normal activity)
infection or drugs

Class IV

No enzyme
N/A
deficiency (60-150%)

Great interest as
genetic markers

Class V

No enzyme
deficiency
(>150%)

No clinical
significance

N/A

Important details
Results in
hereditary
nonspherocytic
hemolytic anemia

Summary
located on the long (q) arm of the X
chromosome at position 28
Generally in males
Females can also be affected provided
both X gene is variant

GENETICS

X-linked recessive disorder

due to more than 400 different missense, point
mutations in G6PD gene, present on long arm of X
chromosome
EXAMPLES:
G6PD-A(+): AsparagineAspartic acid, Class IV
G6PD-A(-): ValineMethionine,
AsparagineAspartic acid, Class III
G6PD-Mediterran: SerinePhenylalanine, Class II
G6PD-Cosenza: ArginineProline, Class II

SIGNS AND SYMPTOMS

nonimmune hemolytic anemia in
response to environmental
triggers
Prolonged neonatal jaundice,
possibly leading to kernicterus
In severe cases, acute renal failure

INFECTION:
Inflammatory response to infection results in
generation of free radicals in macrophages, which
diffuse into red cells causing oxidative damage.

FAVISM: (Italian: fava=broad beans)

Definition: haemolytic response to the
consumption of broad beans.
All individuals with favism show G6PD deficiency.
However, not all individuals with G6PD deficiency
show favism.
Broad beans contain high levels of vicine, divicine,
convicine and isouramil, all of which are oxidants.

JAUNDICE:
resulting
from
impaired
hepatic
catabolism
of heme or
increased
production
of bilirubin

ACUTE RENAL FAILURE:

due to red cells disintegration in the
circulation, causing hemoglobin excretion
directly by the kidneys.
HEINZ BODIES:
are inclusions within red blood cells
composed of denatured hemoglobin.
Oxidation of reduced sulfhydryl groups of
proteins including hemoglobin in red cells
causes their denaturation into insoluble
masses attached to red cell membrane.

G6PD DEFICIENCY & MALARIA

A side effect of G6PD deficiency is that it
confers protection against malaria, in
particular the form of malaria caused by
Plasmodium falciparum, the most deadly form
of malaria.
Basis for this resistance may be a weakening
of the red cell membrane (the erythrocyte is
the host cell for the parasite) such that it
cannot sustain the parasitic life cycle long
enough for productive growth.

DIAGNOSIS

Complete blood count and reticulocyte count; Heinz

bodies can be seen in red blood cells on a blood film
Liver enzymes (to exclude other causes of jaundice)
Lactate dehydrogenase elevated in hemolysis and a
marker of hemolytic severity
Haptoglobin decreased in hemolysis.
Beutler test, also known as the fluorescent spot test,
is a screening test used to identify enzyme defects. It
is a rapid and inexpensive test that visually identifies
NADPH produced by G6PD under ultraviolet light.
When the blood spot does not fluoresce, the test is
positive i.e. G6PD deficiency present.

TREATMENT

The most important measure is PREVENTION avoidance of the drugs and foods that cause hemolysis.
Vaccination against some common pathogens (e.g.
hepatitis A and hepatitis B) may prevent infectioninduced attacks.
In the acute phase of hemolysis, blood transfusions
might be necessary
Dialysis in acute renal failure
Some patients may benefit from removal of the spleen;
splenectomy, as this is an important site of red cell
destruction.
Folic acid should be used in any disorder featuring a
high red cell turnover.

4. Explain the role of glutathione in the

development of hemolytic anemia in
G6PD deficiency.

5. Enumerate drugs that an precipitate

hemolytic anemia among patients
with G6PD deficiency.

 Glutathione
helps maintain the reduced states of sulfhydryl groups in proteins, including
hemoglobin
removes H2O2 via glutathione peroxidase

Accumulation of H202

Decrease RBC lifespan

hemolysis

Commonly used drugs that

produce hemolytic anemia in
patients with G6PD deficiency

ENVIRONMENTAL TRIGGERS
Factors causing Oxidative Stress precipitate clinical
manifestations of G6PD Deficiency.
OXIDANT DRUGS:
Antibiotics: Sulfonamides (such as sulfanilamide,
sulfamethoxazole and mafenide), a few non-sulfa
antibiotics (nalidixic acid, nitrofurantoin, isoniazid,
furazolidone and chloramphenicol)
Antimalarials: primaquine, pamaquine and chloroquine
Antipyretics: aspirin, phenazopyridine and acetanilide
Henna has been known to cause haemolytic crisis in
G6PD-deficient infants.

Why is it that G6PD deficiency have

lesser tendency to contract malaria?
A reduction in the amount of functional glucose6-dehydrogenase appears to make it more
difficult for this parasite to invade red blood
cells.
The P. Falciparum parasite invades the G6PD
deficient cell, but intracellular development is
impaired.

What
complications
of
G6PD
deficiency make DNA analysis best
identification of carriers and patient
diagnosis?
G6PD enzyme testing is primarily performed
when an individual has signs and symptoms
associated with hemolytic anemia and
jaundice.