Glucose-6-Phosphate Dehydrogenase Deficiency: Overview, Pathophysiology, Diagnosis, and Management Introduction: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder affecting red blood cells. G6PD is an enzyme crucial for the pentose phosphate pathway, which helps protect red blood cells from oxidative damage. Deficiency in this enzyme can lead to hemolytic anemia, particularly under oxidative stress. Pathophysiology: G6PD deficiency is caused by mutations in the G6PD gene located on the X chromosome. The enzyme G6PD plays a vital role in the pentose phosphate pathway, producing NADPH, which helps maintain the levels of reduced glutathione. Reduced glutathione is essential for neutralizing reactive oxygen species (ROS) and protecting red blood cells from oxidative damage. In individuals with G6PD deficiency, the reduced ability to produce NADPH results in a decreased capacity to neutralize ROS. This leads to oxidative stress on red blood cells, causing hemolysis, particularly when the cells are exposed to certain triggers. The severity of hemolysis can vary depending on the degree of enzyme deficiency and the type of mutation. Clinical Presentation: Symptoms of G6PD deficiency can range from mild to severe and may include:  Acute Hemolytic Anemia: Characterized by fatigue, pallor, jaundice, dark urine, and an enlarged spleen.  Jaundice: Due to the breakdown of hemoglobin into bilirubin.  Dark Urine: Often due to the presence of hemoglobinuria from the breakdown of red blood cells.  Fatigue and Shortness of Breath: Resulting from the reduced oxygencarrying capacity of the blood. The onset of symptoms is often triggered by oxidative stress, which can be induced by:  Certain Medications: Such as sulfonamides, nitrofurantoin, and primaquine.  Infections: Bacterial or viral infections can exacerbate oxidative stress.  Fava Beans: Consumption of fava beans can trigger hemolysis in affected individuals, a condition known as favism.  Chemicals: Exposure to certain chemicals, including some disinfectants and dyes. Diagnosis: Diagnosis of G6PD deficiency involves several steps:  Clinical History and Physical Examination: Assessing symptoms and potential triggers.  Laboratory Tests: o Complete Blood Count (CBC): May show signs of hemolytic anemia, such as elevated reticulocyte count and low hemoglobin levels. o G6PD Enzyme Activity Assay: Confirms the deficiency by measuring the enzyme activity in red blood cells. This test is typically done when the patient is not experiencing an acute hemolytic episode, as enzyme levels can be normal during acute hemolysis. o Peripheral Blood Smear: Can show bite cells and Heinz bodies, which are indicative of oxidative damage to red blood cells. Management: Management of G6PD deficiency focuses on preventing hemolytic episodes and managing symptoms:  Avoid Triggers: The most crucial aspect of management is avoiding known triggers of oxidative stress. This includes avoiding certain medications, foods like fava beans, and chemicals.  Treatment of Infections: Prompt treatment of infections with appropriate antibiotics can help prevent hemolytic episodes.  Supportive Care: In cases of acute hemolysis, supportive care may include hydration, blood transfusions, and management of symptoms like jaundice and anemia.  Education: Patients should be educated about their condition and the importance of avoiding triggers to prevent hemolytic crises. Prognosis: The prognosis for individuals with G6PD deficiency is generally good if triggers are avoided and the condition is managed appropriately. Most individuals with the condition live normal lives without significant complications. However, severe cases of hemolysis can lead to complications such as severe anemia or kidney damage if not managed properly. Regular follow-up and patient education are important for ensuring long-term health and preventing avoidable complications.