GLUCOSE-6-PHOSPATE DEHYDROGENASE DEFICIENCY GENETICS PRESENTATION BY GROUP A2(MD2) WINDSOR UNIVERSITY SCHOOL OF MEDICINE. IVEREN,FOLA,FLOURISH, ALLISON, ARSLAN,AARON,SHAFFIQ, MUBARAK,GOODNESS.

OBJECTIVES INTRODUCTION/BACKGROUND HISTORICAL PERSPECTIVE CAUSES AND WORLDWIDE PREVALENCE SYMPTOMS DISEASE DIAGNOSIS TREATMENT AND MANAGEMENT FUTURE PERSPECTIVES. REFERENCES AND LITERATURE USED.

INTRODUCTION/BACKGROUND Glucose-6-phosphate dehydrogenase deficiency is an X- linked genetic disorder that mainly affects the Red Blood Cells. There is a deficiency in an enzyme known as Glucose-6- phosphate dehydrogenase which is responsible for a normal RBC life span and for oxidizing processes. This deficiency provokes the premature destruction of RBC which leads to hemolytic anemia and other conditions and this is one of the most common enzyme deficiencies known.

HISTORICAL PERSPECTIVE G6PD was discovered as an outgrowth of an investigation of hemolytic anemia occurring in some individuals treated for malaria with 6- methoxy-8-aminoquinoline drugs. Cordes reported the occurrence of acute hemolysis in such patient in 1926, but 3 decades passed before the mechanism of hemolysis could be understood.

HISTORICAL PERSPECTIVE(CONT’D) The discoveries that led to the recognition of G6PD deficiency were the result of several converge events. According to myths and legends, G6PD deficiency (popularly believed to be favism), was known before the middle ages in Europe. Greek-Roman cults and Pythagoras were known to have forbidden the eating of beans, most probably due to favism.

CAUSES AND WORLDWIDE PREVALENCE A mutation in the G6PD gene cause glucose-6- phosphate dehydrogenase deficiency. This is an X-linked mutation. The gene that codes for G6PD is located in the distal long arm of the X chromosome at the Xq28 locus. This gene provides the instructions required for making the enzyme Glucose-6-Phosphate dehydrogenase. This enzyme is involved in normal processing of carbohydrate. It also protects the red blood cells from the effect of reactive oxygen species.

CAUSES AND PREVALENCE CONT’D This more prevalent in males. An estimated 400 million people worldwide have this deficiency. This occurs most frequently in certain parts of Africa, Asia, and Mediterranean. It affects about 1 in 10 African American males in the United States.

SYMPTOMS Persons with this condition do not display any signs of the disease until their red blood cells are exposed to certain chemicals in food or medicine, or to stress. Symptoms are more common in men and may include: - Dark urine -Enlarged spleen -Fatigue -Pallor -Rapid heart rate -Shortness of breath -Yellow skin color (jaundice)

DISEASE DIAGNOSIS The conversion of Nicotinamide Adenine Dinucleotide Phosphate(NADP) to its reduced form(NADH) in erythrocytes is the basis of diagnosis for the deficiency. This is usually done by the fluorescent spot test. The test is positive if the blood spot fails to fluorescence under ultraviolent light.

TREATMENT AND MANAGEMENT Most Patient diagnosed with this disease doesn’t need any treatment, however because the deficiency cause, breakdown of Red blood Cells leading to Anemia, there are precautions to be taken to avoid the conditions such as: Avoid oxidative drugs such as ( antimalarial drugs, Vitamin K analogues, Sulfonamides, NSAIDS, sulfamethazole etc. Exclusion of Fava beans from their diet. Daily Folic Acid intake. Mesoporphyrin (experimental- heme analogue).

TREATMENT AND MANAGEMENT CONT’D Patient should have a a comprehensive analysis of their blood done Removed all Oxidative agents immediately Based on the type of Anemia, transfusion should be done in extreme Cases Infants with prolong Juandice- administer bili- Light therapy Chronic or severe patients require daily folic acid intake Follow up with a Hematologist and Geneticist

FUTURE PERSPECTIVE G-6-PD deficiency is a genetic disorder which for now there is no cure. Although there is research going on but there is still no absolute result yet. Although some new clinical trials are going on in some parts of Africa. A new clinical trial of antimalarial combination therapy combining chlorproguanil, dapsone, and artesunate is being conducted in some African countries and G6PD deficiency patients are not excluded. G6PD deficiency genotyping.

REFERENCES AND LITERATURE USED