What is glucose-6-phosphate dehydrogenase (G6PD) deficiency?
A variety of factors can trigger acute hemolysis in G6PD-deficient individuals for example ingestion of fava beans (also known as favism), mothballs or anti-malarial drugs. G6PD deficiency is an inherited hemolytic anemia due to a red cell enzyme defect. For the RBC to be fully functional as an oxygen carrier, there are 3 important factors involved. They are the condition of the red blood cell membrane, the metabolic pathways involved in maintaining cell survival as well as the condition of the hemoglobin. There are 4 major metabolic pathways involved and they are interconnected. The key actions of these pathways include energy supply to the system, oxidant reduction of the cell, maintaining haemoglobin in a reduced state and regulation of oxygen release. These pathways use enzymes to convert specific molecules into their intended metabolites for the optimal functioning of the red blood cells.
G6PD is involved in the hexose monophosphate pathway in red blood cell metabolism and functions to convert hydrogen peroxide to water in the erythrocyte. The inheritance is sex-linked, affecting males and carried by females. This disorder is one of the most common disorders worldwide .The degree of deficiency varies and is often mild in black Africans, more severe in Orientals and most severe in Mediterraneans.
Why is glucose-6-phosphate dehydrogenase (G6PD) important?
G6PD deficiency affects the red blood cell metabolism pathway particularly the hexose monophosphate shunt. G6PD is the catalyst in the rate-limiting first step of the pentose phosphate pathway, which uses glucose-6-phosphate to convert nicotinamide adenine dinucleotide phosphate (NADP) into its reduced form, NADPH. In red blood cells, NADPH is critical in preventing damage to cellular structures caused by oxygen-free radicals (e.g., hydrogen peroxide). It does this by serving as a substrate to the enzyme glutathione reductase. Reduced glutathione can be used to convert hydrogen peroxide to water and prevent damage to cellular structures, particularly the cell wall of RBCs since they have limited capacity for repair once mature. When the red cell is challenged by an oxidant stress, for example moth balls in G6PD deficiency, both lipids and red cell membrane proteins become oxidized as there is not enough reduced glutathione produced to convert the increased level of oxidants to water. Hemoglobin denatures and precipitates intracellular to become Heinz bodies. The presence of rigid inclusions causes the red cell to be trapped in the spleen and sometimes splenic macrophages surgically excise the portion of the red cell that contains a Heinz body. In these circumstances, the red cell may escape with a gap, appearing as bite cells. These rigid and fragmented cells may also lead to intravascular hemolysis.
Causes of acute hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency
A variety of infections and drugs can trigger acute hemolysis in G6PD-deficient individuals. Ingestion of fava beans may trigger acute, severe, intravascular haemolysis as a condition known as favism. The glycosides vicine and convicine in fava beans are responsible for hemolysis. They generate aglycones that auto-oxidize and produce free radicals. Other agents that may cause hemolytic anemia in G6PD deficiency include mothballs, infections and other acute illnesses for example diabetic ketoacidosis and oxidative drugs for example antimalarials, analgesics and sulphonamides and sulphones.
Features of glucose-6-phosphate dehydrogenase (G6PD) deficiency
G6PD-deficiency is usually asymptomatic unless triggered by an oxidant. There could be neonatal jaundice too. The acute hemolytic anemia is caused by rapidly developing intravascular hemolysis with hemoglobinuria (blood in the urine). The anemia may be self-limiting as new young red cells are made with near normal enzyme levels.
How do I test for glucose-6-phosphate dehydrogenase (G6PD) deficiency?
General laboratory tests
Between crises the blood count is normal. In a crisis, the FBC would have low hemoglobin level and reticulocytosis and the blood film may show contracted and fragmented cells with bite cells and blister cells which have had Heinz bodies removed by the spleen.
Specific tests
Specific tests include decreased fluorescence in the fluorescence spot test and Heinz bodies may be seen in the reticulocyte preparation particularly if the spleen is absent. DNA analysis will be positive for the gene mutation. Biochemical parameters will show increased serum bilirubin and lactate dehydrogenase levels but reduced serum haptoglobin level.
How is glucose-6-phosphate dehydrogenase (G6PD) deficiency treated?
Treatment and management include removing the underlying cause for example drugs must be stopped for treatment and blood transfusion where necessary for severe anemia. Underlying infections must also be treated and if indicated, splenectomy may be carried out.
Below is the synopsis of glucose-6-phosphate dehydrogenase (G6PD) deficiency:
Definition of glucose-6-phosphate dehydrogenase (G6PD) deficiency treated
An inherited hemolytic anemia due to red cell enzyme defect. X-linked recessive disorder – full expression only seen in males.
Epidemiology of G6PD deficiency
Approximately 5% of the global population.
Signs and symptoms of G6PD deficiency
- Usually asymptomatic
- Acute intravascular hemolytic anemia and hemoglobinuria during crises
- Neonatal jaundice / hyperbilirubinemia
Crises causes of G6PD deficiency
- Fava beans
- Oxidative drugs (antimalarial drugs)
- Antihelminths (mothballs)
- Aspirin in high doses
- Infections
- Sulphonamides
Pathophysiology of G6PD deficiency
Laboratory investigations for G6PD deficiency
Confirmatory / Screening tests
- Supravital staining – presence of Heinz bodies
- Fluorescent spot test screening – reduced fluorescence
- DNA analysis – positive for mutation
Full blood count and Peripheral blood characteristics in crises
Full blood count: ↓ hemoglobin, reticulocytosis.
Peripheral blood smear: Moderate anisopoikilocytosis, polychromatic cells, microspherocytes and bite cells.
Other important investigations and expected results
- ↑ serum bilirubin.
- ↑ lactate dehydrogenase.
- ↓ serum haptoglobin.
Treatment and management of G6PD deficiency
- Stop ingestion of oxidative drugs or fava beans
- Transfuse packed red cells if necessary
- Treat underlying infection if present
- Splenectomy may ameliorate hemolytic anemia in rare chronic hereditary nonspherocytic hemolytic anemia
