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CBL G-6-PD deficiency, biochemistry


Introduction:

➢Reactive oxygen species (ROS)

are molecules formed by partial

reduction of molecular oxygen.

➢Hexose Monophosphate Shunt

(pentose phosphate pathway) is

the main source of NADPH+H

required for the reaction of

many reductases and

hydroxylases.

➢Glutathione reductase and

glutathione peroxidase are

important for removal of

reactive oxygen species as H2O2.

➢H2O2 is powerful oxidant that

produce damage of cellular DNA,

proteins and phospholipids.


G-6-PDdeficiency:

➢Diminished G-6-PD activity lead

to impaired HMP shunt. So No

NADPH- H is found to form G-SH.

➢Reduced glutathione functions

as coenzyme for the enzyme G-

SH peroxidase which protects

RBC's against free radicals as

H2O2 which has toxic effect

cellular DNA, proteins and

phospholipids.

➢Oxidation of membrane proteins

causes the red cells to be rigid

and nondeformable and they are

removed from the circulation by

macrophages by spleen and liver

leading to hemolytic anemia.

➢Although G-6-PD deficiency

occurs in all cells of the affected

individual, it is most severe in

erythrocytes where the pentose

phosphate pathway is only

source of NADPH-H+.
 ➢Also G-6-PD deficiency -

NADPH+H+ -synthesis fatty acid

and cholesterol in the cell

membrane Fragility and

hemolysis of RBCs.

➢Moreover, decreased reduced

glutathione lead to oxidation

and denaturation of RBCs

proteins forming insoluble

masses called Heinz body

attached to red cell membrane.


Precipitating factors include:

➢Infection is the most common

(inflammation produce free

radicals).

➢Oxidant drugs (sulfa-

methoxazole and

chloramphenicol, acetanilide

aspirin & some antimalarial

drugs as primaquine).


Favism:

• some forms of G-6-PD deficiency

are susceptible to hemolysis by

fava beans .

• All patients with favism have G-

6-PDdeficiency but not all

patients with G-6-PD deficiency

are susceptible to hemolysis by

fava beans


G-6-PD deficiency:

➢Definition:

 A genetically inherited disease characterized by increased fragility of RBCs &

hemolysis occurs after the intake of some drugs (aspirin, sulfa &

some antimalarial drugs) or after

intake of fava beans, or after

infections

➢Cause: Deficiency of G-6-PD

enzyme.

➢It is a sex linked disease (affect

males, females are carriers).

Affect 200 million individuals

worldwide.


Diagnosis:

For patient who develop pallor,

jaundice and symptoms of

hemolysis:

• To detect anemia (Complete

blood count)

• To detect hemolysis reticulocyte

count (increased immature

RBCs) and decreased

haptoglobin.

• To detect G-6-PD deficiency

(estimation of enzyme activity

and Heinz body in erythrocyte).


Treatment:

• Avoid precipitating agents (fava

beans & oxidizing drugs),

• treatment of infection

• blood transfusion is done after

crisis.


Case (1):

21 years old male medical student with malaria. He was treated with primaquine. Four
days later, he complained of black colored urine, yellowish discoloration of sclera, pallor.
By investigation, there was low RBCs count, elevated reticulocytes count, red blood cells
with Heinz bodies.

. What is the possible diagnosis?

. What is the name of defective pathway in this patient?

. What is the mechanism of hemolytic anemia in this case?


Case (2):

. A 44 year old man presented to the emergency department with a five day history of
feeling tired and unwell, associated with bouts of vomiting. He also noticed that he had
yellow sclera and dark urine. He denied a history of foreign travel or the usage of herbal
medications or drugs. On further questioning, he recalled consuming two separate meals of
broad beans 48 hours and 24 hours before his symptoms began. On examination, he was
clinically jaundiced with mild pitting oedema of the ankles.

. What is the possible diagnosis?

. What is the name of deficient enzyme?


Data:

https://drive.google.com/file/d/1VZDNVLH8iyN743vzBHADZc3U5Hz1Zxzp/view?usp=drivesdk

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