What is Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

From the Guidelines

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder that affects red blood cells, causing them to break down prematurely when exposed to certain triggers, and it is crucial to avoid oxidant drugs and other triggers to prevent hemolysis, as recommended in the most recent study 1.

Definition and Pathophysiology

G6PD deficiency is an X-linked recessive condition that primarily affects males and is the most common enzyme deficiency worldwide, with over 400 million people affected globally. G6PD is an enzyme that helps protect red blood cells from oxidative damage by maintaining levels of NADPH, which keeps glutathione in its reduced form. When deficient, red blood cells become vulnerable to oxidative stress, leading to hemolysis (cell destruction).

Clinical Presentation and Diagnosis

Common triggers include certain medications (such as antimalarials like primaquine, antibiotics like sulfamethoxazole, and rasburicase), fava beans, infections, and diabetic ketoacidosis. Symptoms range from none to severe hemolytic anemia with jaundice, dark urine, fatigue, shortness of breath, and in extreme cases, kidney failure. Diagnosis involves laboratory tests, including measurement of G6PD enzyme activity, and it is essential to consider G6PD deficiency in infants with significant hyperbilirubinemia, as recommended in 1.

Management and Prevention

Management involves avoiding known triggers, prompt treatment of infections, and in severe cases, blood transfusions. Genetic counseling may be recommended for affected families since this condition is hereditary. Most people with G6PD deficiency can lead normal lives with proper precautions and awareness of triggering factors. It is also crucial to use caution when administering certain medications, such as methylene blue, in patients with G6PD deficiency, as recommended in 1.

Some key points to consider:

• G6PD deficiency is a genetic disorder that affects red blood cells, causing them to break down prematurely when exposed to certain triggers.
• Common triggers include certain medications, fava beans, infections, and diabetic ketoacidosis.
• Symptoms range from none to severe hemolytic anemia with jaundice, dark urine, fatigue, shortness of breath, and in extreme cases, kidney failure.
• Management involves avoiding known triggers, prompt treatment of infections, and in severe cases, blood transfusions.
• Genetic counseling may be recommended for affected families since this condition is hereditary.
• It is essential to consider G6PD deficiency in infants with significant hyperbilirubinemia and to use caution when administering certain medications, such as methylene blue, in patients with G6PD deficiency, as recommended in 1 and 1.

From the Research

Definition and Overview of G6PD Deficiency

• G6PD deficiency is a genetic disorder caused by inherited mutations of the X-linked gene G6PD, making red cells highly vulnerable to oxidative damage and susceptible to hemolysis 2.
• It is one of the most common human enzymopathies, with an estimated 400 million people worldwide carrying a mutation in the G6PD gene that causes deficiency of the enzyme 3.
• The disorder is usually asymptomatic, but individuals with G6PD deficiency can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or are exposed to certain infections or drugs 4.

Causes and Mechanisms of G6PD Deficiency

• G6PD deficiency arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age 4.
• The majority of mutations cause red cell enzyme deficiency by decreasing enzyme stability, and the polymorphic mutations affect amino acid residues throughout the enzyme and decrease the stability of the enzyme in the red cell 5.
• Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity, compromising the stability of the protein, or decreasing the catalytic activity 2.

Clinical Manifestations and Complications of G6PD Deficiency

• Individuals with G6PD deficiency are susceptible to neonatal jaundice, acute hemolytic anemia, and chronic nonspherocytic hemolytic anemia 5, 2.
• Certain medications, such as dapsone, methylthioninium chloride, nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride, can trigger hemolytic anemia in individuals with G6PD deficiency 3.
• Infections and ingestion of fava beans can also trigger acute hemolytic anemia in individuals with G6PD deficiency 2, 4.

Geographic Distribution and Global Health Impact of G6PD Deficiency

• G6PD deficiency correlates remarkably with past/present malaria endemicity, and it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality 2.
• G6PD deficiency is a global health issue, with significant implications for the management of malaria and other diseases 4.
• The geographic distribution of G6PD deficiency is influenced by the relative protection it confers against malaria infection, with higher frequencies of G6PD deficiency in areas with high malaria endemicity 5, 2.