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Glucose-6-Phosphate Dehydrogenase Deficiency

Glucose-6-Phosphate Dehydrogenase Deficiency is a topic covered in the 5-Minute Pediatric Consult.

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Basics

Description

Deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) that leads to increased RBC vulnerability to oxidative stress and may cause hemolytic anemia. Several types of genetic mutations result in either deficient enzyme production or diminished enzyme activity.

  • Although most patients with this deficiency are never anemic and have mild to no hemolysis, the classic manifestation is acute hemolytic anemia in response to oxidative stress.
  • World Health Organization classification of G6PD variants:
    • Class 1: congenital nonspherocytic hemolytic anemia: rare. Chronic hemolysis without exposure to oxidative stressors—splenomegaly in 40%. Affected individuals tend to be white males of Northern European background.
    • Class 2: severe deficiency (1–10% enzymatic activity): oxidative stress–induced hemolysis. Prototype is G6PD-Mediterranean.
    • Class 3: mild deficiency (10–60% enzymatic activity): most common type. Acute hemolytic anemia uncommon occurs only with stressors.
    • Class 4: nondeficient variant (60–100% enzymatic activity): no symptoms, even during oxidant stressors (e.g., G6PD A+ [variant with normal activity]); 20–40% allelic frequency in Africans
    • Class 5: >150% of normal activity
  • Deficient neonates may have hyperbilirubinemia out of proportion to their anemia.
    • May, in part, account for increased prevalence of bilirubin encephalopathy in African Americans. In the United States, ~20% of kernicterus is G6PD related.
    • Should be considered in the evaluation of neonatal hyperbilirubinemia in infants of appropriate ethnicity

General Prevention

  • Avoid drugs and toxins known to cause hemolysis (see “Pathophysiology” section).
  • Prompt follow-up with febrile illness and signs of hemolysis.

Epidemiology

Prevalence

  • Most common of all clinically significant enzyme defects, affecting approximately 400 million people worldwide. ~7.5% of the world’s population carries one or two genes for G6PD deficiency.
  • X linked (Xq28) with almost 400 allelic variants
  • Frequency of different mutations varies by population:
    • Africans: 20–40% of X chromosomes are G6PD A+ (mutant enzyme with normal activity).
    • Sardinians (some regions): 30% have G6PD-Mediterranean (variant with 1–10% enzymatic activity)
    • Saudi Arabians: 13% have G6PD deficiency.
    • African Americans: 10–15% have G6PD A– (mutant enzyme with <30% normal activity).
  • High incidence of mutant genes in some regions may relate to survival advantage against malarial infection (Plasmodium falciparum and Plasmodium vivax).

Genetics

Gene is on the X chromosome (Xq28).

  • Males express the enzyme (mutant or normal) from their single X chromosome (hemizygotes).
  • Female homozygotes (rare) are more severely affected than female heterozygotes.
  • Heterozygote females show variable intermediate expression because of random X inactivation leading to somatic cell mosaicism.

Pathophysiology

  • G6PD catalyzes the production of NADPH that protects RBCs from oxidative damage.
  • Normal G6PD activity is 7 to 10 IU/g hemoglobin. Following exposure to oxidative stress, G6PD-deficient RBCs are destroyed by intravascular hemolysis resulting in hemolytic anemia.
  • Oxidant stressors include infections and chemicals (e.g., mothballs, antimalarials, some sulfonamides, rasburicase, methylene blue). RBCs lose G6PD activity throughout their lifespan; therefore, older cells are more prone to oxidative hemolysis.
  • Normal RBC lifespan of ~120 days is unaffected in unstressed states, even with severe enzyme deficiency but may be shortened during oxidant stress.
  • Hemolysis usually follows stressor by 1 to 3 days, and the nadir occurs 8 to 10 days postexposure.
  • Favism: severe hemolytic anemia in patients with more severe forms of G6PD deficiency that occurs after fava bean ingestion

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Citation

Cabana, Michael D., editor. "Glucose-6-Phosphate Dehydrogenase Deficiency." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617334/all/Glucose_6_Phosphate_Dehydrogenase_Deficiency.
Glucose-6-Phosphate Dehydrogenase Deficiency. In: Cabana MD, ed. 5-Minute Pediatric Consult. 8th ed. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617334/all/Glucose_6_Phosphate_Dehydrogenase_Deficiency. Accessed April 22, 2019.
Glucose-6-Phosphate Dehydrogenase Deficiency. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult. Available from https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617334/all/Glucose_6_Phosphate_Dehydrogenase_Deficiency
Glucose-6-Phosphate Dehydrogenase Deficiency [Internet]. In: Cabana MD, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2019 April 22]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617334/all/Glucose_6_Phosphate_Dehydrogenase_Deficiency.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Glucose-6-Phosphate Dehydrogenase Deficiency ID - 617334 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617334/all/Glucose_6_Phosphate_Dehydrogenase_Deficiency PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -