Glucose-6-Phosphate Dehydrogenase Deficiency PDF

Glucose - 6 - phosphate dehydrogenase (G6PD) deficiency Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  G6PD deficiency G6PD deficiency is the most prevalent enzyme deficiency in the world, over 400 million people are...

Glucose - 6 - phosphate dehydrogenase (G6PD) deficiency Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  G6PD deficiency G6PD deficiency is the most prevalent enzyme deficiency in the world, over 400 million people are G6PD deficient in enzyme activity. The inheritance is sex - linked, affecting males,and carried by females. The female heterozygotes have an advantage of resistance to Falciparum malaria. The main races affected are in West Africa, the Mediterranean, the Middle East and South - East Asia. 1/17/2022 Dr.Sahar Gamal Elbager 2 1/17/2022 Dr.Sahar Gamal Elbager 3  Functions of G6PD Functions of G6PD to reduce nicotinamide adenine dinucleotide phosphate (NADP) to NADPH It is the only source of NADPH NADPH is needed for : 1. The production of reduced glutathione (GSH). 2. Convert the methaemoglobin (oxidized haemoglobin) containing ferric iron Fe 3 + to functionally active reduced haemoglobin (Fe 2 + state) 1/17/2022 Dr.Sahar Gamal Elbager 4  Reduced glutathione (GSH) Reduced glutathione (GSH) is need by RBCs to get red of free radical (H2O2) Deficiency of G6PD renders the red cell susceptible to oxidant stress 1/17/2022 Dr.Sahar Gamal Elbager 5  Hexose Monophosphate Shunt Pathway. 1/17/2022 Dr.Sahar Gamal Elbager 6  Cause of oxidant stress in G6PD deficiency Fava beans (possibly other vegetables) Infections and other acute illnesses (e.g. diabetic ketoacidosis) Drugs: -Antimalarials (e.g. chloroquine) -Sulphonamides -Antibacterial agents (e.g. chloramphenicol) -Analgesics (e.g. aspirin), moderate doses are safe 1/17/2022 Dr.Sahar Gamal Elbager 7  Epidemiology There is a wide variety of normal genetic variants of the enzyme G6PD, the most common being type Type A in black Africans often being mild (10 – 15% of normal activity) in black Africans Type B (Western) more severe More than 400 variants caused by point mutations or deletions of the enzyme G6PD have been characterized that show less activity than normal 1/17/2022 Dr.Sahar Gamal Elbager 8  Clinical features Acute haemolytic anaemia in response to oxidant stress. The acute haemolytic anaemia is caused by rapidly developing intravascular haemolysis with haemoglobinuria The anaemia may be self limiting as new young red cells are made with near normal enzyme levels. Neonatal jaundice. 1/17/2022 Dr.Sahar Gamal Elbager 9  Diagnosis Between crises the blood count is normal. The enzyme deficiency is detected by one of a number of screening tests or by direct enzyme assay on red cells. During a crisis the blood film may show contracted and fragmented cells, bite cells /blister cells Bite cells which have had Heinz bodies removed by theDr.Sahar 1/17/2022 spleen Gamal Elbager 10  Diagnosis Heinz bodies (oxidized, denatured haemoglobin) may be seen in the reticulocyte preparation, particularly if the spleen is absent. There are also features of intravascular haemolysis. 1/17/2022 Dr.Sahar Gamal Elbager 11  Diagnosis Because of the higher enzyme level in young red cells, red cell enzyme assay may give a false normal level in the phase of acute haemolysis with a reticulocyte response. Subsequent assay after the acute phase reveals the low G6PD level. 1/17/2022 Dr.Sahar Gamal Elbager 12  urine samples in an acute episode of intravascular haemolysis Prussian blue -positive deposits of haemosiderin in a urine 1/17/2022 Dr.Sahar Gamal Elbager 13  Blister ’ cells 1/17/2022 Dr.Sahar Gamal Elbager 14  Heinz bodies 1/17/2022 Dr.Sahar Gamal Elbager 15  Heinz bodies 1/17/2022 Dr.Sahar Gamal Elbager 16  Treatment The wrong drug is stopped Treat any underlying infection Blood transfusion undertaken where necessary for severe anaemia. G6PD deficient babies are prone to neonatal jaundice and in severe cases phototherapy and exchange transfusion may be needed. The jaundice is usually not caused by haemolysis but by deficiency of G6PD affecting neonatal liver function. 1/17/2022 Dr.Sahar Gamal Elbager 17  Pyruvate kinase deficiency This is inherited as an autosomal recessive, the affected patients being homozygous or doubly heterozygous. The red cells become rigid as a result of reduced adenosine triphosphate (ATP) formation. The severity of the anaemia varies widely (haemoglobin 4 – 10 g/dL) and causes relatively mild symptoms. 1/17/2022 Dr.Sahar Gamal Elbager 18  Pyruvate kinase deficiency Because of a shift to the right in the oxygen (O2 ) dissociation curve caused by a rise in intracellular (2,3 - DPG). Clinically, jaundice is usual and gallstones frequent. Frontal bossing may be present. The blood film shows poikilocytosis and distorted cells, particularly post - splenectomy. 1/17/2022 Dr.Sahar Gamal Elbager 19  Pyruvate kinase deficiency Direct enzyme assay is needed to make the diagnosis. Splenectomy may improve the anaemia but does not cure it and is indicated in those patients who need frequent transfusions. 1/17/2022 Dr.Sahar Gamal Elbager 20  Thank you 1/17/2022 Dr.Sahar Gamal Elbager 21