G6PD Deficiency Inheritance Pattern
G6PD deficiency is inherited as an X-linked recessive disorder, meaning the gene is located on the X chromosome and primarily affects males, while females are typically carriers. 1, 2
Genetic Basis
- The G6PD gene is definitively X-linked, located on the X chromosome 1, 3
- Males (XY) who inherit one mutated G6PD gene will express the deficiency because they have only one X chromosome 2
- Females (XX) require two mutated copies to be fully affected, making symptomatic disease much rarer in females 2
- Female carriers (heterozygotes) with one mutated gene may have variable enzyme activity due to X-chromosome inactivation (lyonization), occasionally manifesting mild symptoms 3
Clinical Implications of X-Linked Inheritance
- G6PD deficiency occurs at a much higher frequency in males than in females 2
- Affected males will pass the mutation to all their daughters (who become carriers) but to none of their sons 3
- Carrier females have a 50% chance of passing the mutation to each child, regardless of sex 3
- First-degree relatives of patients with G6PD deficiency should be considered for testing 4
Molecular Characteristics
- Over 200 G6PD mutations have been identified, with approximately half being polymorphic and common in various populations 5
- Almost all G6PD mutations are missense mutations causing amino acid replacements that compromise enzyme stability or catalytic activity 5
- Different mutations are characteristic of specific populations: G6PD A-(202A376G) is most common in African populations, while G6PD Mediterranean(563T) is found in Southern Europe, the Middle East, and Indian subcontinent 3, 6
Important Caveat
While G6PD deficiency is overwhelmingly a hereditary X-linked condition, acquired G6PD deficiency can occur in specific clinical settings (such as hyperaldosteronism and diabetes) through biochemical enzyme inhibition mechanisms, though this is phenotypically indistinguishable from inherited deficiency 7