Causes of G6PD Deficiency in a Child
G6PD deficiency is caused exclusively by inherited mutations in the X-linked G6PD gene located on the X chromosome, making it a genetic disorder passed from parents to children. 1, 2
Genetic Mechanism
G6PD deficiency is definitively an X-linked inherited disorder with the following characteristics:
The G6PD gene is located on the X chromosome, meaning males (XY) who inherit one mutated copy will be affected, while females (XX) need mutations on both copies to be fully affected, though heterozygous females can show variable symptoms 3, 2
Over 200 different mutations of the G6PD gene have been identified that cause enzyme deficiency, with approximately half being polymorphic (common in populations) and half being sporadic (rare, spontaneous mutations) 2, 4
Specific mutations are characteristic of certain ethnic populations: G6PD A-(202A376G) is most common in African populations, G6PD Mediterranean(563T) predominates in Southern Europe, the Middle East, and Indian subcontinent, and several other variants are common in Asian populations 3
Inheritance Pattern
The inheritance follows predictable X-linked patterns:
Males inherit the condition from carrier mothers who pass the mutated X chromosome 1, 2
Affected fathers cannot pass the condition to sons (fathers give Y chromosome to sons), but all daughters of affected fathers will be carriers 1
Female carriers may be asymptomatic or symptomatic depending on X-chromosome inactivation patterns (lyonization) 2, 4
First-degree relatives of affected patients should be tested as they have increased risk of carrying the mutation 1
Geographic and Population Distribution
The prevalence reflects evolutionary selection pressure:
Approximately 400-500 million people worldwide carry G6PD deficiency mutations 2, 4
The geographic distribution correlates remarkably with past/present malaria endemicity, as G6PD deficiency provides protection against malaria mortality in heterozygotes, representing a balanced polymorphism 2
Most common in persons of African, Asian, Mediterranean, or Middle-Eastern descent, while rare in populations like Koreans 4, 5
Molecular Pathophysiology
The mutations cause enzyme deficiency through specific mechanisms:
Almost all G6PD mutations are missense mutations causing amino acid replacements that result in deficient enzyme activity 2
Mutations compromise protein stability, decrease catalytic activity, or both, leading to inadequate enzyme function in red blood cells 2
Different mutations cause different levels of enzyme deficiency, with WHO classification assigning classes to various degrees of deficiency and clinical manifestation 4
Important Clinical Distinction
There is no acquired or environmental cause of G6PD deficiency—it is purely genetic. However, clinical manifestations (hemolysis, jaundice) are triggered by environmental oxidative stressors including certain drugs (primaquine, dapsone, rasburicase), fava beans, or infections in genetically susceptible individuals 1, 2, 4