Overview of G6PD deficiency: Pathophysiology, Symptoms, Causes, and More

 

Overview of G6PD deficiency: Pathophysiology, Symptoms, Causes,  and More

What is G6PD deficiency Anemia?

     Glucose-6-phosphate dehydrogenase deficiency anemia is an inherited disorder, and it is a type of hemolytic anemia. If a patient has G6PD deficiency anemia, then he or she may not synthesize this enzyme due to mutation or if they synthesize, then it will be in less amount. 

     G6PD deficiency is a recessive X-linked trait inherited disorder, that's why males are at a high risk to receive it. 

Normal Physiology of G6PD

     Normally, if the oxidative stress is elevated, then it is removed by the functioning of mitochondria, but the RBCs do not have mitochondria. So, that oxidative stress is removed with the help of reduced glutathione, then it is converted into oxidized glutathione. 

     To convert the Oxidized glutathione into reduced form, NADPH is utilized, which is converted into NADP by giving its electrons to oxidized glutathione. If this cycle continues then the NADPH level will decrease to almost zero, and there will be no NADPH, for the reduction of oxidized glutathione.

     An enzyme named Glucose-6-phosphate dehydrogenase, that reduces the NADP to the NADPH form, so that the cycle continues and oxidative stress can be removed continuously.

Pathophysiology of G6PD deficiency

     The gene that is responsible for the enzyme glucose-6-phosphate dehydrogenase is located in the X-chromosome at the Xq28 locus. If a mutation occurs in this gene, then it will lead to either completely no production of the G6PD enzyme or low production. This mutation will lead to the deficiency of G6PD, then that patient will be at risk of developing anemia if an oxidant increases. 

     As the RBCs with less G6PD deficiency are exposed to the high oxidant levels, it causes the cross-linking of reacting Sulfhydryl groups in the globin chain. So, then the denatured forms of membrane-bound precipitates, called Heinz bodies, are formed.

     As these RBCs having Heinz bodies pass through splenic cords, the macrophages pluck out these bodies, then the remaining RBC looks like having a bite called Bite Cell. These bite cells either retain the same shape or can form spherocytes. Both of these cells are trapped in splenic cords and removed by phagocytes.

     G6PD variations related to hemolysis result in misfolding of proteins, making it more susceptible to proteolytic degradation.

Causes of G6PD deficiency

     G6PD is an X-linked recessive trait inherited disorder, so it is transferred from parents to offspring. The male offspring are at a high risk of getting this G6PD deficiency anemia, as the male has sex chromosomes XY, so if the only X chromosome is defective, then it will develop this disorder. But, it's different for females, coz to develop this disorder in females, they must have both mutant X-chromosomes.

Sign and Symptoms

     The signs and symptoms include Increase heartbeat, shortness of breath, dark or yellow-orange urine, fever, fatigue, paleness, dizziness, paleness, and Jaundice. Most of the individuals are generally asymptomatic.

Clinical Features

     The clinical features include Neonatal jaundice or chronic hemolytic anemia, Acute Intravascular hemolysis marked by Anemia, hemoglobinemia, hemoglobinuria. If infection occurs, it can trigger hemolysis, Pneumonia, Viral hepatitis, and Typhoid fever

G6PD deficiency Diagnosis

     The diagnosis of G6PD deficiency is done by simply doing a G6PD deficiency level check. Also others tests, like Complete blood count, Serum hemoglobin test, and Reticulocyte count are done.

G6PD deficiency treatment

     There is no such treatment of g6pd deficiency, but still, its symptoms can be overcome by the removal of the triggers that can elevate the oxidant levels. These triggers include Infection, Medications, or food. If hemolytic anemia can occur, then Oxygen therapy and blood transfusion can be done that can replenish the O2 (Oxygen) and Red blood cell (RBC) levels.

Which Drugs and Food can be avoided in G6PD deficiency?

     The drugs that can cause an increase of oxidant level include Antimalarial, Sulfonamides, Nitrofurantoin, Acetanilid, Furazolidone, Naphthalene, and others. Some cause hemolysis only in the Mediterranean variant.

     The food that generates oxidants is mostly Fava beans. Also, the food that is cross-contaminated with fava beans, Aniline dyes can be prevented from intake.

Conclusion

     To avoid the G6PD deficiency disorder, the first precaution is to test the female before her marriage, so that one can know that, she is a carrier or not. If the precautionary testing is not done, and a newborn baby is given birth with G6PD deficiency. Then, measures should be taken to not elevate the oxidant levels in RBCs, so that individual can live healthy life.