Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency) is an inherited metabolic disorder that leads to hemolytic anemia due to the inability to detoxify reactive oxygen species, affecting over 400 million people globally. The condition is caused by mutations in the G6PD gene located on the X chromosome, with males being more severely affected due to having only one X chromosome. Diagnosis involves blood tests, and treatment may include blood transfusions, antioxidants, and avoidance of triggers such as fava beans and certain medications.

1. Glucose-6-phosphate
Dehydrogenase deficiency
( G6PD Deficiency)
Khan Arbaz Ali

2. Outline
• Introduction
• Definition
• History
• Principle
• Genetics
• Physiology & Pathophysiolgy
• Causes
• Sign and symptoms
• Diagnostic test (DX)
• Treatment (RX)

3. Introduction
• Most common human enzyme defect
• Present in more than 400 million people
world wide
• Distribution similar to malaria
• X-linked, hereditary genetic defect due to
mutations in the G6PD gene
• More than 140 mutations of the G6PD gene
have been identified.

4. Definition
• It is an inherited disease characterized by
hemolytic anemia caused by inability to
detoxify oxidized agents.
• ‘‘G6PD deficiency is an inherited condition in
which the enzyme doesn’t have enough
activity to detoxify (ROS) Reactive oxygen
species especially in RBCs.

5. History
• In 1931 German Biochemist Warburg and
Christian discovered G6PD
• They isolated G6PD enzyme from brewers
yeast
• His deficiency was first reported in 1956 by
Alving at al.

6. Principle
• Glucose 6 phosphate Dehydrogenase (G6PD)
that catalyze the first reaction PPP which
converts Glucose-6p to 6phosphogluconate
and reduces NADP to NADPH.This reaction is
feedback inhibited by NADPH.

7. Genetics:
• The gene that Encode the
G6PD is located on the distal
long arm of the X chromosome
at the Xq28 locus.
• The G6PD gene is 18 kb long
with 13 exons and the G6PD
enzyme has 515 amino acids.
• Most are single-base changes
that result in an amino acid
substitution.

8. Gene variants
• G6PD variants are caused by point mutation in
the G6PD gene.
• Some of their point mutation do not disturb
active site of the enzyme but may or may not
reduce the active site activity of enzyme
• Three possible result of mutation
• Altered catalytic activity
• Decrease stability
• Or alteration in binding affinity for NADP+

9. MODE OF INHERITANCE
MALES have one X chromosomes
so, they will be disease if
they have the affected gene (XY)
FEMALES have 2X chromosomes
May be homozygous or
heterozygous
HOMOZYGOUS: are
disease (XX)
HETEROZYGOUS: are
not disease but: carriers (and
transfer the disease to their
sons)

10. Physiology (Normal functioning)
Glucose 6 phosphate dehydrogenase use NADP as cofactor and convert into NADPH .Oxidized form of glutathione
(GSSH) converted into reduce form of (2GSH) .Glutathione perioxidase catalyze (GSH) into (GSSH) and convert ROS
into water as shown above in diagram.

11. Pathophysiology (Abnormal functioning)
G6PD DEFICIENCY not enough NADPHS are produced so erythrocytes cannot detoxify h2o2 in sufficient quantity hence cell is
deformed due to heinz body formation .

12. Hemolytic anemia
• Anemia develops when
the spleen traps and
destroys red blood cells.
• An anemic response can
occur when G6PD
deficient individual
takes oxidative drugs or
fava beans.
• How it happen look
right side of this slide
In persons, with G6PD deficiency,
oxidative stresses can denature
haemoglobin and cause starts
deposition in RBC
Denatured haemoglobin can be
visualized as Heinz bodies

13. Favism
• Favism usually result of
ingestion of fresh uncooked
fava beans although it can
occur with dried cooked
canned or frozen beans.
• Acute intravassuclar
hemolysis develop within 5-
24 hours after ingestion.
• Fall in hemoglobin is fatal in
severe and acute condition
if blood transfusion is not
performed.
• Vicine is an
alkaloid glycoside found
in fava beans.Vicine is
toxic,oxidant and causing
the disease favism, in
individuals who have a
hereditary loss of
the enzyme glucose-6-
phosphate dehydrogenase

14. Why Erthyrocytes are only affected
• Other cells are also G6PD Deficient
• Malate Dehydrogenase (NADP+) (EC 1.1.1.82)
they have another source of NADPH production
• Superoxide Dismutase (SOD, EC 1.15.1.1)
superoxide (O2
−) radical into either ordinary
molecular oxygen (O2) or Hydrogen peroxide (H2O2)
• Catalase (EC 1.11.1.6) It catalyzes the
Decomposition of hydrogen peroxide
to water and oxygen 2 H2O2 → 2 H2O + O2

15. Causes
• RBCs destruction can be triggered by infections,
certain foods(such as fava beans) and certain
drugs, including:
• Genetic abnormality
• Antimalarial drugs
• Aspirin
• Nitrofuranton
• NSAIDs
• Quinine
• Sulfa drugs

16. Diagnostic tests
• A blood test can be done to check the level of
G6PD
• Others tests maybe done include:
• Bilirubin level
• Complete blood count, including RBCs count
• Haemoglobin – blood
• Haemoglobin – urine
• LDH test

17. Sign and symptoms
• People with this condition do not display any sign of
the disease until their RBCs are exposed to certain
chemicals in food or medicine or stress.
symptoms are more common in men and may include:
• Dark urine
• Enlarged spleen
• Fatigue
• Rapid heart rate
• Shortness of breath
• Palpitations

18. Treatment
• Blood transfusion
• Uses of antioxidant
• Vitamin E and selenium used as antioxidant drugs
• Splenectomy
• Prevention of haemolysis by prompt treatment
infection.
• Avoidance of oxidant drugs and toxin:
• Sulfonamide (drugs)
• Naphthalene (toxin)
• Genetic modified fava beans can be used .