G6PD deficiency management

Overview

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited enzymatic disorder of red blood cells (RBCs), affecting more than 400 million people worldwide.

It is an X-linked recessive genetic disorder in which haemolysis results from oxidative damage to RBCs due to loss of the protective effect of the G6PD enzyme. G6PD plays a critical role in the pentose phosphate pathway by generating nicotinamide adenine dinucleotide phosphate (NADPH), which protects RBCs against oxidative stress. Deficiency of the enzyme increases susceptibility to episodic haemolytic anaemia following exposure to oxidative stress.

Pathophysiology

G6PD deficiency leads to:

• Reduced NADPH production.

• Decreased glutathione regeneration.

• Oxidative damage to haemoglobin.

• Formation of Heinz bodies.

• Splenic removal of damaged RBCs (bite cells).

• Intravascular and extravascular haemolysis.

Risk factors

Risk factors include:

• Male sex.

• Family history of G6PD deficiency.

• African, Mediterranean, Middle Eastern, or Asian ancestry.

• Exposure to oxidative stressors.

Common triggers

Haemolysis may occur following:

• Infection.

OR

• Incriminated drugs such as:

  • sulphonamides

  • chloroquine

  • primaquine

  • proguanil

  • nitrofurantoin

  • dapsone

  • aspirin (high doses)

OR

• Foods such as:

  • fava beans (favism)

Clinical presentation

Most individuals are asymptomatic until exposed to oxidative stress.

Acute haemolytic episode

Patients may present with:

• Pallor.

• Jaundice.

• Dark urine (coca-coloured or cola-coloured urine).

• Fatigue.

• Back pain.

• Abdominal pain.

• Tachycardia.

• Acute anaemia.

Neonatal presentation

Neonates may present with:

• Prolonged neonatal jaundice.

• Increased risk of kernicterus.

Chronic haemolysis

Rare variants may present with:

• Chronic nonspherocytic haemolytic anaemia.

Diagnostic criteria

Diagnosis is based on:

• Clinical history of episodic haemolysis.

AND

• Laboratory evidence of haemolysis.

AND

• Confirmatory G6PD enzyme testing.

Investigations

Perform the following investigations:

• Full blood picture (FBP).

• Peripheral blood smear.

• Reticulocyte count.

• Methaemoglobin reduction (G6PD) test.

• Creatinine.

• Bilirubin.

• Alanine aminotransferase (ALT).

• Lactate dehydrogenase (LDH).

• Quantitative G6PD enzyme assay, where available.

• Blood grouping and cross-matching if blood transfusion is required.

Peripheral blood smear findings

The peripheral blood smear may show:

• Normocytic normochromic anaemia.

• Bite cells.

• Heinz bodies (on supravital stain).

• Occasionally spherocytes.

Management

Management is primarily supportive and includes removal of precipitating factors, supportive care, and treatment of haemolysis.

Non-pharmacological management

• Immediately withdraw the offending drug or other oxidative trigger.

• Treat any underlying infection.

• Avoid known oxidative drugs and foods.

• Ensure adequate hydration.

• Monitor renal function.

Pharmacological treatment

Give:

• folic acid (PO) 5 mg every 24 hours for 1 to 3 months.

AND

• Blood transfusion

In patients with severe anaemia:

• Transfuse packed red blood cells 10 mL/kg body weight.

THEN

• Assess the haemoglobin level AND clinical presentation.

AND

• Repeat transfusion as needed according to the blood transfusion protocol.

AND

• Monitor haemoglobin after transfusion.

Complications

Potential complications include:

• Severe acute haemolytic anaemia.

• Acute kidney injury (acute renal failure).

• Neonatal kernicterus.

• Chronic haemolytic anaemia (rare).

Prognosis

The prognosis is generally excellent if oxidative triggers are avoided.

• Haemolytic episodes are usually self-limited.

• G6PD deficiency is a lifelong condition requiring preventive measures.

Prevention

Preventive measures include:

• Patient education.

• Screening in high-risk populations.

• Avoidance of oxidative drugs.

• Avoidance of fava beans.

• Neonatal screening programmes where available.

• Genetic counselling.

Patient counselling

Advise patients to:

• Inform all healthcare providers that they have G6PD deficiency.

• Carry medical identification indicating their diagnosis.

• Avoid self-medication without consulting a healthcare professional.

• Avoid known oxidative drugs and foods that may precipitate haemolysis.