Wednesday, September 14, 2011

G6PD Deficiency

بسم الله الرحمن الرحيم
(learning issue's note)


Glucose-6-Phosphate Dehydrogenase Deficiency
 
G6PD catalyzes the initial step in the hexosemonophosphate shunt -> protects RBC from oxidant injury
G6PD deficiency:
¢No anemia in steady state
¢Normal reticulocyte counts
¢Decrease RBC survival
¢Associated with chronic hemolytic anemia
Red cell's metabolism pathway
Genetics 
¢G6PD deficiency is transmitted by a mutant gene located on the X chromosome (Xq28) 
¢Fully expressed in men <-hemizygous 
¢Fully expressed in women <- homozygous 
¢Various expression in women <- heterozygous
  eg.a female with 50% normal G6PD: 50% normal RBC & 50% G6PD-deficient RBC 
  
Prevalence & Demographic Distribution
¢Deficiency of G6PD à most common metabolic disorder of RBC 
¢200 million people are affected worldwide 
¢Global distribution; greatest frec.in tropical and subtropical zone 
¢20 % in African Bantu males 
¢12% in African-American males 
¢Male Asian population:
14% in Cambodia
5.5% in south China
2.6% in India
— <1.5% in Japan

 The Enzymes & Its Variant

Enzyme Type
Population usually associated
G6PD B
All
G6PD Mediteranean
Whites (Mediterranean area)
G6PD A+
Africans
G6PD A-
Africans
G6PD Canton
Asians
 
WHO classification based on the magnitude of enzymes deficiency & severity of hemolysis:
Class I: severe enzyme def (<10% of normal) & chronic hemolytic anemia
Class II: severe enzyme def.  intermittent hemolysis
Class III: moderate enzyme def.(10-60% of normal) & intermittent hemolysis
Class IV: no enzyme def.or hemolysis
Class V : increased enzyme activity
  G6PD def. -> decreased leukocyte & platelets activity ->rarely manifest functional impairment (Short survival of leukocytes and platelets)
  
Clinical Manifestation
¢Majority are asymptomatic most of the time
¢G6PD 20% normal act is sufficient for normal RBC function & survival
¢Newborns with intrinsic defect, adult take therapeutic drug/ develop infection à suffer various degrees of hemolysis 
¢2-3 days after administration the drugs :
Ø ↓RBC, ↓Hb  
Ø anemia normochromic normocytic
Ø↑reticulocyte
Ø back pain
ØHemoglobinuria
Ø Jaundice
   

Drugs and chemicals associated with hemolytic anemia in G6PD deficiency
 
Chloramphenicol
Primaquine
Dapsone
Sulfacetamide
Doxorubicin
Sulfametoxazole
Methylene blue
Sulfanilamide
Naphtalene
Sulfapyridine
Pamaquine
Thiazolesulfone
Pentaquine 
Trinitrotoluene (TNT)


Diagnosis
Acute hemolysis  after administration chemical agents --> suspect G6PD def!:
¢Laboratory: ↓Hb, ↓HCT, hemoglobinuria
¢Morphologic RBC alterations:
Irregularly contracted erytrocytes
Bite cells
Heinz bodies
¢Hemolysis in serum
¢↑ serum bilirubin
¢Leukocyte/ PLT : n  
 Evidence family history or drug sensitivity --> screening:
¢Peripheral blood staining -->  Heinz bodies (oxidative denaturation of Hb)
¢Methemoglobin reduction test (G6PD-def.RBC fail to reduce MetHb)
¢Ascorbate-cyanide test (measure perioxidative denaturation of Hb)
Spesific test: Fluorescent spot test (+ in G6PD def.)
 

  Treatment
¢Determined by clinical syndrome
¢Acute hemolysis --> ↓Hb & RBC --> transfusion
¢Avoid exposure to drugs-triggered hemolysis
¢Exchange transfusion in nonspherocytic hemolytic anemia during the first week of life (prevent bilirubin encephalopathy)

Screening
¢Mediterranean populations --> knowing their G6PD status, avoiding oxidant exposures
¢In areas where G6PD def. is common --> screening donor blood for premature infants or neonatus 
 
References:
  • Harmening's Clinical Hematology and Fundamentals of Hemostasis. 4th ed.
  • Wintrobe's Clinical Hematology. 10th ed. 
  • Wintrobe's Atlas of Clinical Hematology. 1st ed. 

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