From the Guidelines
Monitoring for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in relatives, particularly from father to child, is crucial to prevent hemolytic crises, and genetic testing is recommended for at-risk relatives, especially before exposure to oxidative stressors, as stated in the most recent guideline 1.
Inheritance Patterns and Testing
G6PD deficiency is an X-linked recessive disorder, meaning fathers with G6PD deficiency will pass the affected X chromosome to all their daughters (who become carriers) but not to their sons (who receive the father's Y chromosome instead).
- The standard diagnostic test measures G6PD enzyme activity in red blood cells through quantitative spectrophotometric analysis, with results below 60% of normal indicating deficiency.
- Testing should occur when the person is healthy, as false negatives can occur during hemolytic episodes when older red blood cells have been destroyed.
Management and Prevention
Affected individuals should avoid triggers like certain medications (including sulfonamides, antimalarials like primaquine, nitrofurantoin, and some NSAIDs), fava beans, naphthalene (in mothballs), and specific infections.
- Genetic counseling is advisable for families with G6PD deficiency to understand inheritance risks and management strategies.
- Early identification helps prevent potentially severe hemolytic crises by allowing for appropriate precautions and prompt treatment when necessary, as recommended by recent studies 1.
Recent Recommendations
Recent guidelines recommend monitoring without further treatment or addition of oxygen supplementation if needed for minimally symptomatic or asymptomatic patients, and testing for G6PD deficiency in those without known history of methemoglobinemia 1.
- The first line treatment of the symptomatic patient is MB with a starting dose of 1–2 mg/kg of 1% MB to be repeated up to a dose of 5.5 mg/kg if no response after 30 min, as recommended by experts with a high level of consensus 1.
From the Research
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- G6PD deficiency is an X-linked genetic disorder that affects the enzyme responsible for protecting red blood cells from oxidative damage 2, 3, 4, 5.
- The disorder is caused by mutations in the G6PD gene, with over 200 known mutations, and is the most common human enzymopathy worldwide 3, 4.
- G6PD deficiency is often asymptomatic, but can lead to neonatal jaundice, acute hemolytic anemia, and chronic nonspherocytic hemolytic anemia in some cases 2, 3, 4, 5.
Inheritance Pattern
- G6PD deficiency is inherited in an X-linked pattern, meaning that males are more likely to be affected than females 2, 3, 4.
- Female carriers of the mutation can pass it to their sons, who will be affected, and to their daughters, who will be carriers 2, 3, 4.
- Fathers cannot pass the mutation to their sons, but can pass it to their daughters, who will be carriers 2, 3, 4.
Monitoring in Relatives
- Screening programs for G6PD deficiency are undertaken in communities with high prevalence of the disorder 4.
- Early screening can identify at-risk infants and foster early identification, diagnosis, and treatment to eliminate neurotoxicity 6.
- Mandatory universal screening for G6PD deficiency, including surveillance and hospital-based risk assessment tools, can help identify affected individuals and prevent complications 6.
Clinical Manifestations
- The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, usually triggered by an exogenous agent such as fava beans, certain drugs, or infections 2, 3, 4, 5.
- Some G6PD variants can cause chronic hemolysis, leading to congenital non-spherocytic hemolytic anemia 4.
- G6PD deficiency can also lead to severe hyperbilirubinemia, which can cause bilirubin-induced neurologic dysfunction, acute bilirubin encephalopathy, and kernicterus if not promptly recognized and treated 6.