Snapshot A 25-year-old man with Mediterranean ancestry presents with jaundice. He also reports being unusually tired and believes this may be due to his recent recovery from mononucleosis. He was found to be anemic with a hemoglobin of 9 g/dL. His peripheral blood smear revealed bite cells and Heinz bodies. 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 Pathophysiology G6PD affects the pentose phosphate (hexose monophosphate) pathway this 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 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 is thought to decrease risk of severe malaria Genetics inheritance pattern X-linked mutations G6PD gene encoding the G6PD enzyme Prognosis natural history of disease typically asymptomatic until exposed to oxidative stressors 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 jaundice Studies Labs complete blood count and reticulocyte count peripheral smear bite cells Heinz bodies hemolysis labs ↑ indirect bilirubin ↓ haptoglobin ↑ lactate dehydrogenase urine hemoglobinuria G6PD activity assays indication 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 Differential Gilbert syndrome jaundice at birth (rather than delayed onset of jaundice) normal G6PD enzyme activity Hereditary spherocytosis spherocytosis seen on peripheral blood smear Treatment Conservative avoid oxidative stressors Medical blood transfusion indication if severe Complications Recurrence of acute hemolysis