G6PD Deficiency -glucose 6-phosphate dehydrogenase -in redox metabolism of all aerobic cells -important in red cells as the

only source of NADPH that directly or via glutathione (GSH) to defend oxidative stress -RBC in fact have higher G6PD activity than other tissue, so no clinical impact if no exogenous agents

Genetic Considerations -X-linked -male only one gene (hemizygous): normal or G6PD-deficient -female: normal, deficient (homozygous) or intermediate (heterozygous) -will have highly variable of G6PD-normal to deficient cells ratio and clinical expression -mutation cause stability of the protein, G6PD activity as red cell aged -a variantchronic nonspherocytic hemolytic anemia CNSHA -more severe instability or affinity for G6P Epidemiology -up to 20% -resistant against Plasmodium falciparum malaria -different G6PD variant in different part: SEA G6PD Vianchan and G6PD Mahidol Clinical Manifestations -majority asymptomatic lifetime -risk of neonatal jaundice (NNJ) -rarely present at birth, peak at day 2-3 -may severe in premature, infection, environmental factors (naphthalene-camphor balls) -more severe if with mutation of UGT1A1 (Gilbert syndrome) -if not txkernicterus and permanent neurologic damage -risk of acute hemolytic anemia (AHA) -due to fava beans, infections, drugs -start with malaise, weakness, abdominal or lumbar pain -after hours to 2-3djaundice, dark urine (hemoglobinuria)

-onset abrupt esp with favism -anemia -from moderate to extremely severe -usually normocytic normochromic -with hemoglobinemia, hemoglobinuria, LDH, or absent plasma haptoglobin -blood film: anisocytosis, polychromasia, spherocytes -most typical bizarre poikilocytes: RBC with unevenly distributed hemoglobin (hemighosts) and had part of them bitten away (bite cells / blister cells) -classical test: stain with methyl violet, reveal Heinz bodies (precipitates of denatured hemoglobin, indicate oxidative damage to RBC) -LDH and unconjugated bilirubin = also extravascular hemolysis -most serious complication of AHA acute renal failure -in adult, rare in children -once AHA over, always full recover

-CNSHA variant: always male, history of NNJ, with anemia, unexplained jaundice or gallstones -spleen may enlarged -anemia severity variable from borderline to transfusion-dependent -anemia: normo-macrocytic with reticulocytosis -bilirubin and LDH -may affect granulocytes too susceptibility to bacterial infection

Laboratory Diagnosis -semiquantitative methods for screening -quantitative methods for diagnostic -females heterozygotes may missed Treatment -avoid exposure -no fava beans, careful in drug prescribing -normally no specific treatment needed -if anemia severe blood transfusion -if acute renal failure hemodialysis, will full recovery -in CNSHA: regular folic acid supplements, regular hematologic surveillance -may need regular blood transfusion, institute iron chelator -may consider splenectomy