G6pd deficiency and its manifestations ppt

This is a ppt on g6pd deficiency for medical students

1. G6PD Deficiency

2. Definition Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked hereditary enzyme defect affecting red blood cells. Results in episodic haemolysis following oxidative stress (infection, drugs, or fava beans). Most common enzyme deficiency worldwide (~400 million people).

3. Genetics X-linked recessive → mainly males affected. Carriers (females) may show mild or intermittent haemolysis. High prevalence in malaria-endemic areas (Africa, Middle East, South & Southeast Asia, Mediterranean). Protective against falciparum malaria (evolutionary advantage ).

4. Pathophysiology G6PD enzyme is part of the hexose monophosphate (pentose-phosphate) pathway → produces NADPH. NADPH maintains reduced glutathione (GSH), which protects RBCs from oxidative damage. Deficiency → ↓ NADPH → ↓ GSH → oxidative stress damages Hb & RBC membrane. Denatured Hb → Heinz bodies → membrane damage → intravascular & extravascular haemolysis.

5. Risk factors Drugs: antimalarials (primaquine), sulphonamides, nitrofurantoin, dapsone, quinolones. Foods: fava beans (favism). Infections: bacterial, viral (most common trigger). Others: diabetic ketoacidosis, naphthalene (mothballs).

6. Clinical features Usually asymptomatic until oxidative stress occurs. Acute haemolytic episode: Sudden pallor, jaundice, dark urine (haemoglobinuria). Back or abdominal pain. Tachycardia, fatigue, dyspnoea. Neonatal jaundice – may cause kernicterus. Chronic haemolysis (rare, in severe variants).

7. Investigations CBC: normocytic anaemia, ↑ reticulocytes. Blood film: bite cells, blister cells, Heinz bodies (shown with supravital stain). Haemolysis labs: ↑ unconjugated bilirubin, ↑ LDH, ↓ haptoglobin. Direct Coombs (DAT): negative. G6PD enzyme assay: confirmatory test (may be falsely normal during crisis).

8. This is an image showing peripheral blood smear findings

9. Management Avoid oxidative triggers (drugs, fava beans). Treat underlying infection. Supportive care: Hydration. Blood transfusion if severe. Folic acid supplementation in chronic haemolysis. Neonatal jaundice: phototherapy ± exchange transfusion.

10. Paroxysmal Nocturnal Haemoglobinuria Acquired clonal disorder of haematopoietic stem cells. Characterised by complement-mediated intravascular haemolysis, cytopenias, and thrombosis. Caused by deficiency of glycosyl-phosphatidylinositol (GPI)-anchored proteins that protect cells from complement attack.

11. Genetics Rare disease (approx. 1–2 per million per year). Affects both men and women; typically presents in young to middle adulthood. May arise de novo or evolve from aplastic anaemia or myelodysplasia.

12. Pathophysiology Somatic mutation in the PIGA -phosphatidylinositol glycan anchor gene (on the X chromosome) in a multipotent stem cell. Leads to defective GPI anchor synthesis → loss of surface proteins such as CD55 (decay accelerating factor) and CD59 (membrane inhibitor of reactive lysis) RBCs without these proteins are highly sensitive to complement-mediated lysis. Results in: Intravascular haemolysis → haemoglobinuria. Bone marrow failure (due to stem-cell defect). Thrombosis (due to platelet activation and free Hb binding nitric oxide).

13. Clinical features Triad: Intravascular haemolysis Venous thrombosis (especially hepatic/portal/cerebral veins) Bone marrow failure (pancytopenia) Haemoglobinuria: dark “cola-coloured” urine, especially morning samples. Symptoms: fatigue, jaundice, pallor, dyspnoea, abdominal pain, dysphagia (smooth muscle dystonia). Thrombosis: main cause of death in PNH.

14. Lab findings CBC: normocytic anaemia ± pancytopenia. Haemolysis markers: ↑ LDH ↑ unconjugated bilirubin ↑ reticulocytes Urine: haemoglobinuria, haemosiderinuria. Urine: haemoglobinuria, haemosiderinuria. Direct Coombs (DAT): negative (non-immune haemolysis). Flow cytometry: diagnostic test showing absence of CD55/CD59 on RBCs and granulocytes.

15. Management Supportive therapy: Transfusions as needed. Folic acid supplementation. Iron replacement if iron-deficient. Anticoagulation for thrombosis Targeted therapy: Eculizumab (anti-C5 monoclonal antibody) – prevents complement-mediated lysis. Ravulizumab – long-acting C5 inhibitor (newer). Bone-marrow transplantation: only curative option (for severe cases or marrow failure).

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