Glucose 6 Phosphate Dehydrogenase Test (G6PD)

Glucose 6 Phosphate Dehydrogenase Test (G6PD) – Why am I having this test?

Glucose 6 Phosphate Dehydrogenase Test is used to check for a condition in which your body does not have enough of the G6PD enzyme (G6PD deficiency).

The G6PD enzyme helps prevent damage to your red blood cells. Some people are born with a deficiency of this enzyme.

G6PD deficiency is a condition that is passed from parent to child (inherited). For people with a G6PD deficiency, certain illnesses or medicines can lead to the loss of red blood cells (hemolytic anemia). In newborns, this may show as yellowing of the skin (jaundice). The G6PD test may be done to help find the cause if these conditions occur.

What is being tested?

There are several different testing methods available for G6PD testing. Some tests measure the levels of G6PD in your blood. Other tests look for G6PD deficiency in your DNA.

What kind of sample is taken?

A blood sample is required for this test. It is usually collected by inserting a needle into a blood vessel.

How are the results reported?

Your test results will be reported as values. Your health care provider will compare your results to normal ranges that were established after testing a large group of people (reference values). Reference values may vary among labs and hospitals. For this test, a common normal reference value is:

• 10.1–14.1 international units per gram of hemoglobin.

If genetic testing is done, a normal G6PD sequencing would show no mutation.

What do the results mean?

G6PD enzyme results that are below normal values may indicate G6PD deficiency.

G6PD enzyme results that are above normal values may indicate a number of health conditions. These may include:

• Pernicious anemia.
• Ongoing (chronic) blood loss.

G6PD sequencing (genetic testing) can help you and your health care provider understand the severity of your condition.

Talk with your health care provider about what your results mean.

Questions to ask your health care provider

Ask your health care provider, or the department that is doing the test:

• When will my results be ready?
• How will I get my results?
• What are my treatment options?
• What other tests do I need?
• What are my next steps?

Summary

• The glucose-6-phosphate dehydrogenase (G6PD) test is used to check for a condition in which your body does not have enough of the G6PD enzyme.
• For people with a G6PD deficiency, certain illnesses or medicines can lead to hemolytic anemia. The G6PD test may be done to help find the cause if that occurs.
• G6PD enzyme results that are below normal values may indicate G6PD deficiency.
• Talk with your health care provider about what your results mean.

Detailed Info on Glucose 6 Phosphate Dehydrogenase Test

12 Interesting Facts of Glucose 6 Phosphate Dehydrogenase Test

1. Deficiency of G6PD (glucose-6-phosphate dehydrogenase) includes a group of X-linked disorders rendering RBCs susceptible to hemolysis when exposed to oxidative stress (eg, infection, fava beans, certain medications); it is characterized by acute hemolytic episodes and/or severe newborn jaundice
2. More common in African, Middle Eastern, Mediterranean, and Asian populations
3. Most people with a G6PD enzyme defect are asymptomatic throughout life
4. Typical finding includes antiglobulin-negative nonspherocytic hemolytic anemia with bite cells on peripheral smear triggered by exposure to a known oxidative drug, infection, or fava beans
5. Severe neonatal hyperbilirubinemia requiring exchange transfusion in an infant of African, Middle Eastern, Mediterranean, or Asian descent is likely related to G6PD deficiency
6. Screening test for G6PD deficiency is the semiquantitative fluorescent spot test; positive test result implies less than 10% to 20% of normal G6PD activity in RBCs 
7. Gold standard test to confirm G6PD deficiency is quantitative analysis of G6PD enzymatic activity 
8. Obtain screening and confirmatory tests for G6PD deficiency 2 to 3 months after acute hemolytic event, transfusion, or treatment of newborn jaundice to avoid false-negative results 
9. Prevention of hemolysis involves education and avoidance of triggers in patients with known G6PD deficiency
10. Treatment of severe hyperbilirubinemia secondary to G6PD deficiency in newborns requires aggressive phototherapy and potentially erythrocyte exchange transfusion
11. Acute hemolysis secondary to G6PD deficiency is self-limited; most cases will resolve with removal of oxidative stress
    • Occasionally RBC transfusion is required if patient becomes symptomatic from anemia or hemoglobin level falls below 7 g/dL 
12. Patients with G6PD deficiency have a normal life expectancy if newborn jaundice and acute hemolytic episodes are effectively treated 

Pitfalls

• G6PD deficiency is occasionally encountered in patients with other RBC defects (eg, sickle cell anemia); it can complicate management of these other disease processes 
• Presence of other diseases affecting erythrocyte metabolism or membrane stability in people with G6PD deficiency may result in more severe acute hemolytic events and/or neonatal jaundice
• Acute hemolysis that occurs while a patient is taking a known oxidative drug is an indication to discontinue the medication until G6PD deficiency is excluded

• Deficiency of G6PD (glucose-6-phosphate dehydrogenase) includes a group of X-linked disorders rendering RBCs susceptible to hemolysis when exposed to oxidative stress (eg, infection, fava beans, certain medications) 
• Clinical presentation varies from neonatal jaundice to acute and chronic hemolytic anemias, depending on specific genetic defect

Classification

• Based on WHO classification
  • Class I
    • Severe deficiency in the functional amount of the enzyme G6PD
    • Associated with chronic nonspherocytic hemolytic anemia
    • Uncommon and occurs among all populations 
  • Class II
    • Severe deficiency with less than 10% of residual G6PD activity 
    • Common and associated with intermittent acute hemolytic anemia
    • More common in Asian and Mediterranean populations 
  • Class III
    • Moderate deficiency with 10% to 60% of residual G6PD activity 
    • Common and associated with hemolysis secondary to oxidant stress
    • Affects 10% of black males in the United States 
    • Frequently occurs in areas where malaria is found 
  • Class IV
    • Normal G6PD activity with functional levels in the 60% to 150% range 
    • Rare and lacking clinical significance
  • Class V
    • Increased activity greater than 150% 
    • Rare and lacking clinical significance
• Based on clinical presentation
  • Acute hemolytic anemia
    • Hemolysis presents 24 to 72 hours after exposure to oxidative stress and resolves spontaneously within 14 days
    • Precipitants of hemolytic crisis include:
      • Drug-related oxidative stress attributed to: 
        • Antimalarials
        • Sulfonamides
        • Sulfones
        • Nitrofurantoin
        • Ciprofloxacin
        • Antipyretic analgesics
      • Other chemicals, such as naphthalene (found in moth balls) and 2,4,6-trinitrotoluene (found in explosives) 
      • Infectious agents 
      • Clinical disorders (eg, DKA, myocardial infarction) 
  • Favism
    • Characterized by acute hemolytic anemia approximately 24 hours after fava bean ingestion 
    • Anemia and hemoglobinuria are more severe with fava bean exposure than with drug- or infection-related G6PD hemolysis
    • Splenic sequestration of RBCs is more common with fava-induced hemolytic anemia
  • Newborn jaundice
    • Indirect jaundice usually presents within 1 to 4 days of life, though typically within the first 24 hours 
    • Newborn jaundice presentation is not usually associated with significant anemia 
    • Occurs more frequently in G6PD-deficient premature infants
  • Chronic congenital nonspherocytic hemolytic anemia 
    • Some variants of G6PD deficiency cause chronic anemia that typically presents in infancy and childhood and is distributed among all populations
    • These rare cases arise from sporadic independent genetic mutations and result in:
      • Severe neonatal jaundice
      • Chronic nonspherocytic hemolytic anemia, reticulocytosis, gallstones, and splenomegaly
      • Oxidative stress–induced recurrent acute hemolytic crisis that requires transfusions

Clinical Presentation

History

• Most people with G6PD deficiency are not aware of their status and are asymptomatic throughout life
• Neonatal jaundice from G6PD deficiency typically presents within the first 24 hours of life 
• Family history may indicate G6PD deficiency, severe newborn jaundice or recurrent jaundice, splenomegaly, and/or cholelithiasis
• Recent medical history in a patient with acute hemolysis may be positive for severe newborn jaundice or recurrent jaundice, splenomegaly, and/or cholelithiasis
• History of exposure to drug or substance (eg, fava beans), 24 to 72 hours before examination, is associated with onset of hemolysis in people with G6PD deficiency 
• During an acute hemolytic episode, symptoms include:
  • Jaundice
  • Fatigue and weakness
  • Hematuria
  • Abdominal pain
  • Back pain
  • Concurrent infectious symptoms (eg, fever)

Physical examination

• Examination findings are usually normal
• During acute hemolysis, expect the following:
  • Tachycardia
  • Pallor
  • Jaundice
  • Scleral icterus
  • Splenomegaly

Causes

• X-linked recessive transmission 
• Most common enzyme disorder worldwide; about 8% of the global population carries 1 or more mutations for G6PD deficiency 
  • Over 140 specific mutations have been reported in coding sequence for G6PD, accounting for numerous recognized variants of disease 
• Females can phenotypically express G6PD deficiency through genetic mosaicism even when heterozygous for the genetic defect 
• Oxidative drugs that precipitate hemolysis in people with G6PD deficiency include: 
  • Primaquine and pamaquine
  • Sulfonamides and sulfones
  • Dapsone
  • Nitrofurantoin
  • Ciprofloxacin, moxifloxacin, norfloxacin, and ofloxacin
  • Acetanilide and aspirin
  • Nalidixic acid
  • Phenazopyridine
  • Flutamide
  • Methylene blue
  • Probenecid
  • Vitamin K
• Chemicals that precipitate hemolysis in people with G6PD deficiency include: 
  • Naphthalene (found in moth balls)
  • 2,4,6-trinitrotoluene (found in explosives)
• Infectious agents that cause oxidative stress include:
  • Influenza A virus 
  • Cytomegalovirus 
  • Hepatitis A and B viruses 
  • Salmonella, Escherichia coli, and β-hemolytic streptococci 
  • Rickettsiae
• Activities and clinical disorders that precipitate hemolysis in people with G6PD deficiency include: 
  • DKA
  • Myocardial infarction
  • Strenuous exercise
  • Infection
• Foods that precipitate hemolysis in people with G6PD deficiency
  • Fava beans are the main culprit; isolated case reports exist for other foods

Risk factors and/or associations

Sex

• Males are affected more frequently than females 

Genetics

• X-linked recessive transmission

Ethnicity/race

• Some geographic populations have a higher prevalence of genetic defects in G6PD gene that lead to enzyme deficiency 
  • African descent: up to 39%
  • Middle Eastern descent: 8% to 39%
  • Southeast Asian descent: 8% to 22%
  • Central and Southern Pacific Island descent: up to 7%
  • Southern European descent: up to 3%
• Variants of G6PD deficiency causing the most severe disease appear most often in Mediterranean populations 
• Black males in the United States are affected at a prevalence of approximately 10% 
• G6PD deficiency is found most commonly in geographic areas with the highest rates of malaria

Diagnostic Procedures

Primary diagnostic tools

• History and physical examination usually suggest the diagnosis
  • Signs/symptoms of acute anemia coexisting with hemoglobinuria after ingestion of fava beans or a potentially hemolytic drug point strongly to G6PD deficiency 
• CBC, peripheral smear, reticulocyte count, bilirubin level, and direct antiglobulin tests are first obtained in clinical setting of acute hemolysis and significant neonatal jaundice 
• If history, physical examination, and blood cell count findings are suggestive of G6PD deficiency, further testing for specific disease is warranted after resolution of acute hemolytic crisis (2-3 weeks after acute hemolytic event)
  • Specific testing for G6PD deficiency is indicated in setting of antiglobulin-negative acute hemolytic anemia that is triggered by a known oxidative drug, infection, or exposure to fava beans, particularly if: 
    • Patient is of African, Mediterranean, or Asian descent
    • Patient has positive family history of recurrent jaundice, anemia, or splenomegaly; cholelithiasis; or G6PD deficiency
  • Specific testing for G6PD deficiency is indicated in jaundiced newborns with: 
    • Indirect hyperbilirubinemia greater than 95th percentile within first 24 hours of life 
    • Severe conjugated hyperbilirubinemia and African, Mediterranean, or Asian descent
    • Family history of severe neonatal jaundice in a sibling 
• Rapid semiquantitative tests are the initial step in diagnostic screening 
  • Fluorescent spot test
  • Positive semiquantitative assay result requires definitive diagnosis with quantitative analysis of G6PD activity 
• Gold standard is quantitative measurement of total percentage of G6PD enzymatic activity 
• False-negatives on both screening and confirmatory tests can be reported when measuring G6PD enzymatic activity in clinical settings where young RBCs are prevalent (owing to the relatively higher degree of enzymatic activity in younger RBC populations), particularly as follows: 
  • If the reticulocyte count is high
    • During acute episode of hemolysis
    • Other diseases characterized by elevated reticulocyte counts
      • Chronic hemolytic anemia
      • Renal disease
      • Ongoing blood loss
  • In neonates, who generally have a younger RBC population
  • After RBC transfusion

Laboratory

• CBC
  • Findings include nonspherocytic hemolytic anemia during active hemolysis
  • Normocytic-normochromic anemia is moderate to severe (hemoglobin level less than 2.5 g/dL is rare) 
  • Anemia not typically present in otherwise asymptomatic patients outside of hemolytic crisis
• Peripheral smear 
  • Signs of hemolysis with abnormal RBC morphology are noted during an active G6PD hemolytic event 
    • Bite cells
    • Other poikilocytes
    • Anisocytosis
• Reticulocyte count
  • Elevated 4 to 7 days after an acute hemolytic event 
  • Peaks at 30% or greater 
  • Heinz bodies appear in reticulocytes in active disease 
• Bilirubin level
  • Increased indirect/unconjugated bilirubin level during hemolysis
• Direct antiglobulin test (direct Coombs test) 
  • Sample should be negative for antibodies
• Semiquantitative screening test
  • Fluorescent spot test/Beutler test 
    • Detects degeneration of nicotinamide adenine dinucleotide phosphate to reduced form in RBCs 
    • Positive result (for presumptive G6PD deficiency) is indicated when blood spot fails to fluoresce under UV light 
      • Positive result implies less than 10% to 20% of normal G6PD activity in RBCs 
    • Test is fast, sensitive, and inexpensive 
  • Reported as normal or deficient
  • Screening test does not reliably identify heterozygous females, because X-linked mosaicism leads to partial deficiencies 
  • Not reliable during active disease
• Quantitative analysis of G6PD enzymatic activity
  • Spectrophotometric assay measures quantitative G6PD activity 
  • Reported as percentage of total normal enzyme activity
  • Obtain during disease remission; not reliable during active disease
• Molecular analysis
  • Costly and not usually necessary for diagnosis
  • Only method to definitively diagnose heterozygous females after false-negative quantitative and semiquantitative testing 
  • Used for prenatal screening
• Other laboratory tests that are commonly ordered but not necessary to confirm diagnosis include:
  • Urinalysis
    • In patients with hemolysis, sample is positive for blood on dipstick (hemoglobinuria due to presence of urinary hemosiderin) but negative for RBCs on microscopy
  • Lactate dehydrogenase level
    • Elevated levels during acute hemolytic events
  • Serum haptoglobin level
    • Low levels with intravascular hemolysis

Differential Diagnosis

Most common

• Acquired 
  • Immune-mediated acute hemolytic anemia
    • Causes include:
      • Idiopathic
      • Autoimmune disorders (eg, systemic lupus erythematosus)
      • Infections (eg, viral infections)
      • Malignancies
      • Drugs (eg, penicillin)
      • Transfusions
    • Differentiated by positive direct antiglobulin test result and predominance of spherocytes on peripheral smear
  • Microangiopathic hemolytic anemia
    • Common causes include:
      • Thrombotic thrombocytopenic purpura
        • Characterized by fever, thrombocytopenic purpura, and microangiopathic hemolytic anemia with renal and neurologic dysfunction
        • History and physical examination help distinguish this disorder from G6PD deficiency
        • CBC shows anemia and thrombocytopenia
        • Differentiated by many schistocytes on peripheral smear, normal to slightly increased prothrombin time/partial thromboplastin time, fibrin split products, positive D-dimer assay result, and fibrinogen level within reference range
      • Hemolytic uremic syndrome
        • Cause of renal failure; associated with microangiopathic antiglobulin-negative hemolytic anemia
        • Most common causes are shigella and Escherichia coli toxins
        • History and physical examination help to distinguish this disorder from G6PD deficiency
        • Differentiated by elevated BUN and serum creatinine levels, severe anemia and thrombocytopenia, schistocytosis, fibrinogen level within reference range, prothrombin time/partial thromboplastin time, and positive D-dimer assay result
        • Renal biopsy can confirm diagnosis
      • Disseminated intravascular coagulation
        • Complex, multifactorial process, mediated by complement activation and consumption of coagulation factors, that results in both microangiopathic clotting and hemorrhage simultaneously
        • Occurs as a complication of another underlying critical illness, resulting in shock and multisystem organ dysfunction
        • History and physical examination help differentiate this disorder from G6PD deficiency
        • CBC shows severe anemia and thrombocytopenia
        • Differentiated by extremely elevated prothrombin time/partial thromboplastin time, low fibrinogen level, increased fibrin split products, and positive D-dimer assay result
      • Prosthetic valves
        • Differentiated by history and physical examination and predominance of schistocytes on peripheral smear due to mechanical damage of RBCs
  • Infectious
    • Malaria
      • Plasmodial species are introduced by Anopheles mosquitoes into circulation and direct RBC parasitization results in lysis and splenic sequestration
      • Presents with fever and associated jaundice, intravascular hemolysis, and hemoglobinuria
      • Differentiated by direct visualization of parasite in RBCs on thick and thin peripheral blood smears
    • Babesiosis
      • Babesia species are introduced by ticks and cause a malarialike illness characterized by fever and hemolytic anemia
      • Diagnosis is occasionally evident by direct visualization of pear-shaped protozoa in erythrocytes on peripheral smear
      • Differentiated by IgM or IgG Babesia species microtiters
    • Clostridium perfringens infections
      • Septic abortions and intra-abdominal infections containing toxin-producing Clostridium perfringens cause septicemia with resultant hemolysis and brisk acute hemolytic anemia
      • Fever and other signs of disseminated intravascular coagulopathy accompany this clinical presentation
      • Differentiated by history and physical examination along with demonstration of circulating Clostridium perfringens toxin
  • Paroxysmal nocturnal hemoglobinuria
    • Initial manifestation of this rare disease is hematuria that occurs in the morning with insidious progression to other clinical manifestations of the disease
    • Main clinical manifestations are antiglobulin-negative hemolytic anemia, thrombophilia, and bone marrow failure
    • Differentiated by history and progression of disease to venous thrombosis and pancytopenia
• Hereditary
  • Membranopathies
    • Hereditary spherocytosis
      • Autosomal dominant disorder of erythrocyte membrane structure causing spherical RBCs that are prone to splenic sequestration and extravascular hemolysis
      • Predominantly a chronically compensated hemolytic anemia with an increased mean corpuscular hemoglobin concentration
      • Howell bodies are visible in some erythrocytes
      • Positive family history (in 75% of patients) and predominance of spherocytes on peripheral smear with negative direct antiglobulin test result are supportive of diagnosis 
      • Differentiated with abnormal osmotic fragility test showing hemolysis of incubated RBCs
  • Hemoglobinopathies
    • Thalassemia
      • Heterogeneous group of anemias resulting from defects in hemoglobin synthesis that result in chronic microcytic anemia with episodic intravascular hemolysis
      • Similar ethnic and regional distribution as in patients with G6PD deficiency
      • If diagnosis is in question, hemoglobin electrophoresis (for β-thalassemia) or genetic studies (for α-thalassemia) will confirm
      • Differentiated by hypochromia, microcytosis, and target cells on peripheral smear
    • Sickle cell disease
      • Inherited disorder of hemoglobin structure resulting in fragile sickle-shaped erythrocytes that are prone to intravascular hemolysis and splenic sequestration
      • If diagnosis is in question, hemoglobin electrophoresis will confirm sickle cell disease
      • Differentiated by pathognomonic sickle cells observed on peripheral smear

Treatment Goals

• Manage with discontinuation of precipitating agent or treatment of clinical condition responsible for oxidative stress
• Prevent hemolysis through patient education and trigger avoidance
• Treat newborn hyperbilirubinemia secondary to G6PD deficiency
• Treat anemia as needed

Disposition

Admission criteria

Acute hemolytic crisis

Acute renal failure

Infants with hyperbilirubinemia in the 95th percentile or greater on nomogram require admission for phototherapy and monitoring 

Criteria for ICU admission

• Hemolytic anemia requiring transfusions
• Renal failure requiring dialysis

Recommendations for specialist referral

• Manage patients with diagnosed or suspected G6PD deficiency in consultation with hematologist
• Patients with diagnosed G6PD deficiency require consultation with genetic counselor
• Patients with renal failure require consultation with nephrologist

Treatment Options

Discontinue precipitating agent or treat clinical condition responsible for oxidative stress and subsequent hemolysis 

Acute hemolysis secondary to G6PD deficiency is most often short-lived and does not require treatment 

Rarely, infants and children require transfusions of RBCs in response to an acute hemolytic event 

Newborns may require phototherapy or exchange transfusion for hyperbilirubinemia 

• Expedient management of hyperbilirubinemia in the newborn period is essential to avoid kernicterus and irreversible neurologic damage

Folic acid may be used for patients with chronic hemolysis or nonspherocytic hemolytic anemia 

Drug therapy

• Folic acid
  • Maintenance therapy is indicated in patients with chronic hemolysis or nonspherocytic hemolytic anemia
    • Folic Acid Oral tablet; Children 1—3 years: 0.15 mg PO once daily.
    • Folic Acid Oral tablet; Children 4—8 years: 0.2 mg PO once daily.
    • Folic Acid Oral tablet; Children 9—13 years:  0.3 mg PO once daily.
    • Folic Acid Oral tablet; Adult and Adolescent pregnant females: 0.6 mg PO once daily.
    • Folic Acid Oral tablet; Adults and Adolescents >= 14 years: 0.4 mg PO once daily.

Nondrug and supportive care

Identify and discontinue medication or agent responsible for precipitating acute hemolytic event 

In newborns, hyperbilirubinemia from G6PD deficiency is treated like hyperbilirubinemia from other causes in the newborn 

• Indications for phototherapy and exchange transfusion are based on gestational age, weight, and current age (day of life). Consider other risk factors for hemolysis in making treatment decisions, given individual circumstances (eg, possibility of ABO blood type incompatibility, rate of bilirubin rise, clinical status) 
  • Early in treatment course, close clinical monitoring regarding need for exchange transfusion is indicated with every bilirubin assessment (every 4-12 hours) 
  • In general, if bilirubin level is in 95th percentile or greater, based on American Academy of Pediatrics nomograms, hospitalize infant and treat with phototherapy; exchange transfusion is indicated 

IV fluid

• Administer to infants and children with inadequate oral intake or urine output in the setting of hyperbilirubinemia
• Administer to patients with severe hemolysis and worsening renal function in an effort to protect against acute tubular necrosis

Procedures

Phototherapy for neonates with hyperbilirubinemia

General explanation

• Exposure of infant to UV light converts trans-bilirubin to water-soluble cis-bilirubin, which is more readily excreted

Indication

• Trigger for initiation of phototherapy in the newborn period is based on American Academy of Pediatrics nomogram

Exchange transfusion for severe neonatal jaundice or severe hemolytic anemia 

General explanation

• Patient’s blood is removed; appropriately typed and crossmatched donor blood is infused through central line
• Rapidly increases hemoglobin level with less risk of fluid overload than simple transfusion 
• Newborns with known G6PD deficiency are considered at high risk for kernicterus 

Indication

• Severe hyperbilirubinemia in neonate
  • Trigger for exchange transfusion is based on American Academy of Pediatrics exchange nomogram 
    • Bilirubin levels greater than 15 mg/dL for term infants in first 2 days of life
    • Bilirubin levels greater than 19 mg/dL on days 3 through 7
    • Bilirubin levels greater than 25 mg/dL after day 7
• Need for increased oxygen-carrying capacity secondary to acute hemolysis
  • Indications for transfusion are based on individual symptoms and underlying medical condition
  • Immediately transfuse if hemoglobin level is less than 7 g/dL 
  • Transfuse if hemoglobin level is less than 9 g/dL and there is ongoing brisk hemolysis (as evidenced by continued hemoglobinuria) 

Blood transfusion for severe hemolytic anemia

General explanation

• Appropriately typed and crossmatched donor blood is infused through peripheral or central line

Indication

• Need for increased oxygen-carrying capacity secondary to acute hemolysis
• Symptomatic anemia (eg, fatigue, tachycardia, tachypnea, dyspnea on exertion, postural hypotension, impaired mentation) in euvolemic patient regardless of hemoglobin level 
• Immediately transfuse if hemoglobin level is less than 7 g/dL 
• Transfuse if hemoglobin level is less than 9 g/dL and there is ongoing brisk hemolysis (as evidenced by continued hemoglobinuria) 

Contraindications

• Fluid overload

Comorbidities

• Acute hemolysis or neonatal jaundice from G6PD deficiency can be more severe with unrelated coinherited disorders such as: 
  • Sickle cell anemia
  • Hereditary spherocytosis
  • Thalassemia
  • Pyruvate kinase deficiency
  • Congenital dyserythropoietic anemia
  • Gilbert syndrome

Complications

• Severe neonatal jaundice
  • Can lead to kernicterus, neurologic damage, and death if untreated
• Hemolytic crisis
  • Brisk hemolysis and severe anemia can result in congestive heart failure
• Splenomegaly
• Gallstones
• Renal failure
  • Rare complication, even in presence of massive hemoglobinuria 
  • Acute renal failure is more common with fava-induced G6PD hemolysis 
  • Acute tubular necrosis is a rare complication of G6PD-related hemolysis and concomitant viral hepatitis 
• Death
  • Can be caused by neonatal jaundice or acute hemolytic anemia, if they are not effectively treated

Prognosis

• Patients with G6PD deficiency have normal life expectancy if newborn jaundice and acute hemolytic episodes are effectively treated 

Screening

At-risk populations

• Neonatal screening for G6PD deficiency is recommended for: 
  • Children with family history of G6PD deficiency
  • Children from a high-incidence geographic area or ethnic background
• WHO recommends screening cord blood in countries with high prevalence of disease; defined as a rate of 3% to 5% or more in males 
• Neonatal screening is not performed routinely in the United States 

Screening tests

• Several methods of molecular analysis are available for prenatal screening to identify specific G6PD mutations 
• Confirm any positive cord blood screening test result with a quantitative G6PD test 

Prevention

• Prevention involves avoidance of hemolytic episodes through education about disease and avoiding disease triggers
  • People with known G6PD deficiency and breastfeeding mothers with high-risk infants should avoid oxidative triggers, such as fava beans
• Infants (especially infants in high-risk cultures):
  • Avoid exposure to herbal teas, folk remedies, or any medications that may cause an oxidative stress (direct or indirect via breastfeeding)
  • Avoid exposure to clothes stored in moth balls
• Genetic counseling is recommended before pregnancy for parents who are affected with G6PD deficiency or have family history of known G6PD deficiency

References

1: Cappellini MD et al: Glucose-6-phosphate dehydrogenase deficiency. Lancet. 371(9606):64-74, 2008 Reference