Snapshot A 13-year-old African-American boy presents to his pediatrician for jaundice. He states that he had tried some new Mediterranean food at school today. A day later, he felt fatigued and tired easily after minimal activity and reported back pain. On physical exam, he has scleral icterus. His hemoglobin was found to be 8 g/dL with increased reticulocyte count, increased indirect bilirubin, and decreased haptoglobin. He is given 1 unit of blood. Introduction Clinical definition glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that causes an intrinsic hemolytic anemia Epidemiology Prevalence 7.1% worldwide most common enzyme disorder of erythrocytes Demographics more severe in males than females common in areas where malaria is endemic sub-Saharan Africa Middle East Southeast Asia Mediterranean regions Pacific islands Genetics inheritance pattern X-linked mutations G6PD gene encoding the G6PD enzyme ETIOLOGY Pathophysiology G6PD affects the pentose phosphate (hexose monophosphate) pathway generates nicotinamide dinucleotide phosphate (NADPH), which protects red blood cells against oxidative stress in red blood cells (without mitochondria), this pathway is the only source of NADPH acute hemolytic anemia following exposure to oxidative stressors primaquine dapsone nitrofurantoin sulfa drugs infections fava bean ingestion oxidative stressors cause rapid depletion of reduced glutathione resulting in precipitation of hemoglobin (manifested as Heinz bodies) erythrocyte membrane damage, both extravascular and intravascular hemolysis G6PD deficiency thought to decrease risk of severe malaria Presentation Symptoms primary symptoms neonatal hyperbilirubinemia on day 2-4 acute hemolytic anemia following exposure to precipitants, typically within 24-72 hours after ingestion fatigue jaundice dark urine back pain Physical exam inspection jaundice kernicterus is rare Studies Labs complete blood count and reticulocyte count peripheral smear bite cells (degmacytes) Heinz bodies hemolysis labs ↑ indirect bilirubin ↓ haptoglobin ↑ lactate dehydrogenase urine hemoglobinuria G6PD activity assays indications screening fluorescent spot test most sensitive methemoglobin reduction test Quantitative assays indications confirmation of diagnosis a normal G6PD level immediately after hemolysis does not rule out G6PD deficiency spectrophotometry analysis molecular diagnosis (DNA analysis) Differential Gilbert syndrome jaundice at birth (rather than delayed onset of jaundice) normal G6PD enzyme activity Hereditary spherocytosis spherocytosis seen on peripheral blood smear Disease Peripheral Smear Findings Thalassemia Target cells B12 deficiency Hypersegmented neutrophils Folic acid deficiency Hypersegmented neutrophils G6PD deficiency Heinz bodies and bite cells Asplenia Howell-Jolly bodies Mechanical destruction Schistocytes Microangiopathic hemolytic anemia Schistocytes Hereditary spherocytosis Spherocytes Autoimmune hemolysis Spherocytes Treatment Conservative avoid oxidative stressors Medical blood transfusion indications if hemoglobin < 7 g/dL without hemolysis if hemoglobin < 9 g/dL with hemolysis phototherapy indication neonatal hyperbilirubinemia Complications Recurrence of acute hemolysis Prognosis Natural history of disease typically asymptomatic until exposed to oxidative stressors