Deficiency G6PDD The glycolytic pathway is the main source of energy ATP The hexose monophosphate shunt pathway provides the main source of reduced nicotinamide adenine ID: 550337
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Slide1
Glucose-6-Phosphate Dehydrogenase Deficiency(G6PDD)Slide2
The glycolytic pathway is the main source of energy (ATP)
The
hexose monophosphate ‘shunt’ pathway provides the main source of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which maintains reduced glutathione (GSH) and protects haemoglobin and the membrane proteins against oxidant damage. Slide3
Genetics1. Sex-linked recessive mode of inheritance by a gene located on the X chromosome (similar to hemophilia).
2.
Disease is fully expressed in hemizygous males and homozygous females.,there is an advantage of resistance to falciparum
malaria in heterozygous females.Slide4
Pathogenesis- Red
cell integrity impaired, especially on exposure to oxidant drugs, oxidant response to infection and chemicals.
Oxidation of hemoglobin and of sulfhydryl groups in the membrane.- Oxidized hemoglobin precipitates to form Heinz bodies which are plucked out of the red cell leading to hemolysis and
“
bite cell
”
and
“
blister cell
”
morphology.Slide5
WHO Classification of G6PD VariantsSlide6
Clinical FeaturesEpisodes of hemolysis
may be produced by:
• Drugs. • Fava bean (broad bean): ingestion or exposure to pollen from the bean’s flower (favism
)
•
Infection.
symptoms develop 24
–
48 hr after a patient has ingested a substance that has oxidant properties
,
The degree of hemolysis varies with( the inciting agent, the amount ingested, and the severity of the enzyme deficiency).
The
enzyme is abundant and more stable in younger RBCs. The associated
reticulocytosis
produces a compensated hemolytic process. Slide7
PRECIPITATING FACTORSAntimalarials: primaquine, quinine,
chloroquine
Antibiotics - nitrofuantoin, furazolidine, cotrimoxazole, Nalidixic acid, Chloramphenicol,Others :
Vitamin K – large doses
Naphthalene (moth balls)
Benzene, Methylene blue
Probenecid
Acetyl salicylic acid (aspirin)
Fava beans
Septicemia and viral hepatitis
Diabetic ketoacidosisSlide8
1. Drug-induced hemolysisa. Typically in African-Americans but also in Mediterranean types
c. Acute self-limiting hemolytic anemia with
hemoglobinuriad. Heinz bodies in circulating red cellse. Blister cells, fragmented cellsf.
Reticulocytosis
g. Hemoglobin normal between episodes.Slide9
2. Favism
This results from oxidative products derived from 2
glycosidic compounds, vicine and convicine, which are hydrolyzed to divicine and
isouramil
, ultimately producing
hydrogen peroxide
and other reactive oxygen products.
Acute life-threatening hemolysis, often leading to acute renal failure, associated with Mediterranean.
Blood transfusion is required.Slide10
3. Neonatal jaundiceInfants may present with pallor, jaundice (can be severe and produce kernicterus)and dark urine. When a pregnant woman ingests oxidant drugs, they may be transmitted to her G6PD-deficient fetus, and hemolytic anemia and jaundice may be apparent at birth.
Occasionally exposure to naphthalene (mothballs), aniline dye, marking ink, or a drug. Slide11
Chronic nonspherocytic hemolytic anemia
Occurs mainly with sporadic
inheritance it variable but can be severe with transfusion dependence and intense neonatal presentation(NNJ)
Persons with G6PD B
‾
(Mediterranean) enzyme deficiency occasionally have chronic hemolysis, and the hemolytic process may worsen after ingestion of oxidant drugs.
Splenectomy
is of little value in these types of chronic hemolysis.Slide12
LABORATORY FINDINGS.-Blood
film:RBCs
reveal Heinz bodies (precipitated hemoglobin. Because cells containing these inclusions are rapidly removed from the circulation, they are not seen after the first 3–4 days of illness. The blood film reveals a few fragmented and polychromatophilic cells (bluish, large RBCs), representing reticulocytosis
(5
–
15%).Slide13
DIAGNOSISThe diagnosis depends on direct or indirect demonstration of reduced G6PD activity in RBCs.
By direct measurement
, enzyme activity in affected persons is ≤10% of normal. Immediately after a hemolytic episode, reticulocytes and young RBCs predominate. These young cells have significantly higher enzyme activity than do older cells. Testing may therefore have to be deferred for a few weeks before a diagnostically low level of enzyme can be shown. Slide14
Satisfactory screening tests are based on - decoloration of methylene blue,
- reduction
of methemoglobin- fluorescence of NADPH
G6PD variants also can be detected by
electrophoretic
analysis
.Slide15
Management1. Avoidance of agents that are deleterious in G6PD deficiency.
2.
Education of families and patients in recognition of food prohibition (fava beans), drug avoidance, heightened vigilance during infection and the symptoms and signs of hemolytic crisis (orange/dark urine, lethargy, fatigue, jaundice).3. Indication for transfusion of packed red blood cell in children presenting with acute hemolytic anemia:a. Hemoglobin (
Hb
) level below 7 g/dl
b. Persistent
hemoglobinuria
and
Hb
below 9 g/dl.
4
.
Chronic
nonspherocytic
hemolytic anemia (NSHA):
•
In patients with severe chronic anemia: transfuse red blood cells to maintain
Hb
level (8
–
10 g/dl) and iron chelation when needed.