What is the diagnostic approach for G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency?

Diagnostic Approach for G6PD Deficiency

Screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is strongly recommended before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds. 1

Who Should Be Tested

G6PD deficiency testing should be prioritized for:

• Patients from high-prevalence regions:

  • Africa
  • Mediterranean region
  • Middle East
  • Southeast Asia
  • Oceania 2

• Patients with specific demographic risk factors:

  • Males with ancestry from high-prevalence regions (X-linked disorder)
  • Black men and women (GdA- variant found in 10-15%) 1
  • Men from Mediterranean, India, and Southeast Asia (Gdmed variant) 1

• Clinical scenarios requiring testing:

  • Before starting oxidant drugs (dapsone, primaquine, sulfonamides) 1, 2
  • Patients with unexplained hemolytic anemia
  • Neonates with severe hyperbilirubinemia, especially from high-risk ethnic groups 3
  • HIV-infected patients upon entry into care 1

Diagnostic Testing Algorithm

1. Initial Qualitative Screening:

   • Qualitative G6PD screening test to identify deficiency 1
   • This identifies patients with severe deficiency (typically <30% of normal activity)

2. Confirmatory Testing:

   • Full gene sequencing of G6PD gene for definitive diagnosis 1
   • Quantitative G6PD enzyme activity measurement by spectrophotometric method 4

3. Classification of Severity:

   • Severe deficiency: <10% enzyme activity
   • Moderate deficiency: 10-30% enzyme activity
   • Mild deficiency: 30-60% enzyme activity 5

Special Testing Considerations

• Timing of Testing:

  • Avoid testing during or immediately after acute hemolytic episodes (may give false normal results)
  • For accurate results, test when patient is in stable condition 4

• Female Heterozygotes:

  • Due to X-chromosome inactivation, females may have intermediate enzyme levels
  • Quantitative testing is essential for females to detect intermediate deficiency 6
  • Point-of-care quantitative tests can identify females with <70% normal activity 6

• Laboratory Methods:

  • Spectrophotometric assay is the gold standard for quantitative measurement 4
  • Point-of-care quantitative tests (e.g., STANDARD™ G6PD test) show excellent sensitivity and specificity 6

Clinical Manifestations to Support Diagnosis

Look for history of:

• Neonatal jaundice
• Episodic hemolysis after exposure to:
  • Certain foods (fava beans being most common)
  • Medications (sulfonamides, antimalarials, NSAIDs)
  • Infections 4
• Dark urine (hemoglobinuria) during hemolytic episodes
• Pallor and jaundice occurring 24-72 hours after exposure to triggers 4

Important Caveats and Pitfalls

• False Normal Results:

  • Recent hemolytic episodes may give false normal results due to younger RBCs with higher enzyme activity
  • G6PD testing during acute hemolysis may be misleading 4

• Interference with Other Tests:

  • G6PD deficiency affects reliability of HbA1c testing for diabetes diagnosis
  • In patients with G6PD deficiency, only plasma glucose criteria should be used for diabetes diagnosis 1

• Treatment Considerations:

  • Methylene blue is contraindicated in G6PD deficiency for treating methemoglobinemia 1
  • Primaquine requires G6PD testing before administration due to risk of severe hemolysis 2

By following this diagnostic approach, clinicians can effectively identify G6PD deficiency and prevent potentially life-threatening hemolytic episodes, especially before administering oxidant medications.