Glucose-6-phosphate dehydrogenase deficiency (G6PD) is intravascular hemolytic anemia. It is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an identified oxidative stressor that causes damage to red blood cells (RBCs) which lack sufficient NADPH.
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Epidemiology and Etiology
- Found in Malarial Endemic regions; Mediterranean, African, Middle Eastern descent
- Present exclusively in males as it is X-linked Recessive
- Females can be silent carriers
- Mutation in the Glucose-6-phosphate dehydrogenase(G6PD) enzyme
- A single-base change that results in a single amino-acid substitution
- Mutation lowers the half-life of the enzyme
- G6PD deficiency results in a defect of the Pentose Phosphate Shunt during glycolysis
- Inheritance is X-linked Recessive (band Xq28)
- G6PD is the rate-limiting enzyme in the Pentose Phosphate Pathway
- G6PD enzyme is responsible for
- Oxidation of glucose-6-phosphate
- Reduction of nicotinamide adenine dinucleotide phosphate (NADP+) to NADPH
- NADPH maintains glutathione in its reduced form
- Reduced glutathione is needed to neutralize oxidative metabolites
- In RBCs, this is the ONLY pathway that produces NADPH.
- Thus, a lack of G6PD results in a deficiency in NADPH and increased oxidative damage.
- Oxidative stressors can denature hemoglobin and cause intravascular hemolysis.
- Extravascular hemolysis would be due to splenic clearance of the deformed RBCs.
Common oxidative stressors
- History of a trigger for the oxidative stress
- Episodic Symptoms of Anemia
- Shortness of Breath
- Flow murmur (best heard at upper sternal borders)
- Intravascular Hemolysis
- Hemoglobinuria (cola-colored urine) – Hematuria
- Neonate (Males)
- Prolonged pathological jaundice/icterus (See Neonatal jaundice)
G6PD Deficiency: Clinical Pathology by Carlo Raj, MD
Suspected in cases of episodic hemolytic symptoms.
- ↓ Hb
- ↑ Retics
- ↑ LDH
- ↓ Haptoglobin
- ↑ Bilirubin
- Peripheral Blood Smear
- Heinz Bodies
- Bite Cells
- Beutler test
- Done 2–3 weeks after an acute episode
- quantifies NADPH/G6PD levels
- Avoid oxidative stressors: infections, drugs, fava beans in the diet
- During Hemolysis
- If Hb < 9 with hemolysis – Blood Transfusion
- Neonatal Jaundice – Phototherapy or exchange transfusion
- Splenectomy considered in rare cases of chronic hemolytic anemia
- Hemolytic Anemia: Hemolytic Anemias encompasses anemia due to a shortened half-life of the RBC. The causes include extravascular ( extrinsic/intrinsic) or intravascular. G6PD is an extravascular, intrinsic type.
- Sideroblastic Anemia: It is microcytic anemia in which the bone marrow produces sideroblasts (ring-shaped blood cells) due to the inability of the body to place iron properly into hemoglobin. It presents with abnormal iron studies as well as splenomegaly.
- Sickle Cell Disease: A hereditary hemoglobinopathy resulting in hypoxia and anemia. They share demographics however, sickle cell disease is a chronic hemolytic disorder whereas G6PD deficiency is episodic and less severe.