What are the chances of having Glucose-6-phosphate dehydrogenase (G6PD) deficiency in females?

G6PD Deficiency in Females: Prevalence and Risk Assessment

G6PD deficiency affects approximately 1.9% of females compared to 6.6% of males, with the prevalence varying significantly based on ethnicity and geographic origin. 1

Prevalence and Inheritance Pattern

• G6PD deficiency is an X-linked genetic disorder, primarily affecting males who are hemizygous (having only one X chromosome), but can also affect females who are either homozygous or heterozygous with skewed X-chromosome inactivation 2
• The overall global prevalence is estimated at approximately 400 million people worldwide, making it one of the most common human enzymopathies 2
• In specific populations, prevalence rates vary significantly:
  • African variant (GdA-) is found in 10-15% of Black men and women 3
  • Mediterranean variant (Gdmed) is more common in individuals from Mediterranean regions, India, and Southeast Asia 4

Female-Specific Considerations

• While traditionally considered a predominantly male disease, G6PD deficiency can manifest clinically in females through several mechanisms 1:
  • Homozygous females (with mutations on both X chromosomes)
  • Heterozygous females with skewed X-chromosome inactivation (Lyon phenomenon)
  • Studies have shown that female patients are often underdiagnosed due to the misconception that G6PD deficiency is exclusively a male disease 1

Clinical Manifestations in Females

• Female newborns can present with severe neonatal hyperbilirubinemia related to G6PD deficiency, similar to male infants 5
• Clinical features that suggest G6PD deficiency in females include:
  • Jaundice within the first 24 hours of life
  • Severe hyperbilirubinemia with regenerative hemolytic anemia
  • Poor response to phototherapy
  • Family history or ethnic origin from high-prevalence regions 5

Diagnostic Considerations

• The American Academy of Family Physicians recommends mandatory screening for G6PD deficiency upon entry into healthcare for individuals with predisposing racial or ethnic backgrounds 3
• Screening is particularly important before starting therapy with oxidant drugs that can trigger hemolysis 3
• Diagnostic approaches include:
  • Qualitative screening tests for initial assessment 3
  • Quantitative G6PD testing for confirmation and before administration of certain medications like tafenoquine 3

Risk Factors and Complications

• Females with G6PD deficiency may experience:
  • Acute hemolytic anemia triggered by oxidative stress (medications, infections, or fava beans) 2
  • Neonatal jaundice requiring intervention 5
  • Menorrhagia (heavy menstrual bleeding) in reproductive-age women 6
• The severity of clinical manifestations depends on:
  • The specific G6PD variant (Mediterranean variants typically cause more severe reactions than African variants) 7
  • The degree of enzyme deficiency 2
  • Environmental triggers 2

Family Screening and Genetic Counseling

• First-degree relatives of patients with G6PD deficiency should be tested 3
• Family investigations often reveal previously undiagnosed G6PD deficiency in parents 5
• Molecular characterization can improve diagnostic accuracy, especially in cases with co-inheritance of other red cell disorders 8

Warning Signs and Management

• Signs of hemolysis requiring immediate medical attention include:
  • Dark or reddish urine 4
  • Back or abdominal pain 3
  • Jaundice 4
  • Fatigue and pallor 7
• Immediate discontinuation of any potentially hemolytic medication is recommended if signs of hemolysis occur 3