G-6-PD (Glucose-6-phosphate dehydrogenase) is an enzyme present in the RBC. Deficiency of this enzyme leads to shortening of the red-cell life span and hereditary non-spherocytic hemolytic anemia. It is inherited as an X-linked disorder.

Mechanism of Hemolysis: The life span (particularly of older RBCs) is shortened particularly during drug administration and infection. Drug induced hemolysis in G-6-PD deficient cells is accompanied by formation of Heinz bodies due to inability to reduce NADP+ to NADPH at a normal rate. Hence hemoglobin is denatured and destroyed by the spleen.

The normal enzyme is designated as G-6-PD B. Many variants of G-6-PD have been detected all over the world. G-6-PDdeficiency is common among certain Chinese populations, South-east Asia, West Africa, Kurdish Jews and African-American males. It is suggested that high frequency of G-6-PD deficient genes in many population confers resistance to malaria. This advantage seems to be limited to female heterozygotes

Clinical Features: Individuals who inherit the common (polymorphic) forms of G-6-PD deficiency, such as G-6-PD A- or G-6-PD Mediterranean usually show no clinical manifestations.

The major clinical feature is hemolytic anemia in males usually the anemia is episodic, but some variants may cause congenital non-spherocytic hemolytic anemia. In general, hemolysis is associated with stress, drug ingestion, infection, newborn period and in some individuals – exposure to fava beans. Drugs to be avoided in G-6-PD deficiency are – Furazolidone, Nalidixic acid, Nitrofurantoin, Phenylhydrazine, Primaquine, sulfacetamide, sulfamethoxazole, sulfapyridine and chloramphenicol. Chemicals to be avoided are Methylene blue, Naphthalene, TNT.

There is a difference in severity of reaction to the same drug by different individuals with the same G-6-PD variant as well as different variants. Typically, an episode of drug-induced hemolysis begins 1 to 3 days after drug ingestion. Heinz bodies appear in RBCs and Hemoglobin drops rapidly. Dark urine may occur due to hemoglobinuria. Within 4 to 6 days, reticulocyte count increases

Hereditary non-spherocytic hemolytic anemia manifests as chronic hemolytic anemia, jaundice, splenomegaly, gallstones and ulcers.

Investigations: Varying degree of anemia and reticulocytosis (Hereditary non spherocytic hemolytic anemia) is seen. In absence of hemolysis, the LM morphology of enzyme deficient cells is normal.

In drug-induced hemolysis and in splenectomized patients, Heinz bodies may be present

Other laboratory parameters of hemolysis such as increased level of serum bilirubin, decreased haptoglobin and increased serum LDH may be seen.

Diagnosis of enzyme deficiency is by demonstration of decreased enzyme activity. Difficulty may arise when a patient with G-6-PD deficiency of the A - type has a hemolytic episode. As the older, more enzyme deficient cells are removed from the circulation and replaced by young cells, the level of enzyme begins to rise towards the normal. In such situations, suspicion of G-6-PD deficiency may be considered due to reticulocytosis. Centrifugation of blood followed by testing of the most dense, reticulocyte depleted red cells can be employed in such individuals. Also, family studies and repeating the test again after the red cells have become older is useful.

Screening of hetrozygotes by enzyme assays may be difficult due to presence of normal red cells coexisting. Here, histochemical demonstration of individual red cell enzyme activity is useful such as ascorbate cyanide test. PCR based analysis of mutation is possible and prenatal diagnosis of G-6-PD deficiency can be offered by this technique.

Differential Diagnosis :- Unstable hemoglobinopathy
- Other enzyme defects such as GSH synthetase deficiency

Treatment

G-6-PD DEFICIENT INDIVIDUALS SHOULD AVOID DRUGS THAT INDUCE HEMOLYTIC ANEMIA.
If hemolysis occurs as a result of drug ingestion or infection, transfusion may be required if rate of hemolysis is rapid. In patients with hemoglobinuria, good urine flow should be maintained to prevent renal damage.

Newborns with jaundice due to G-6-PD deficiency may require phototherapy and even exchange transfusion.

Patients with hereditary non-spherocytic hemolytic anemia due to G-6-PD deficiency usually do not require treatment. Splenectomy is generally ineffective. In some cases, frequent transfusions may be required.