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G6PD deficiency

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Overview

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary red cell enzyme deficiency and is inherited in an X-linked recessive manner.

G6PD is involved in the reduction of NADP to NADPH which is used to generate reduced glutathione. Reduced glutathione protects red cells from oxidative damage. A deficiency in G6PD leads to less NADPH, and less glutathione, leading to increased oxidative stress and haemolysis.

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

Epidemiology

  • More common in the Mediterranean, Africa, and the Middle East
  • It often presents as severe neonatal jaundice

Haemolytic Crises

A haemolytic crisis describes acute, severe haemolytic anaemia. Drugs known to trigger haemolytic crises are:

  • Primaquine
  • Nitrofurantoin
  • Quinolone antibiotics
  • ‘Sulf’ drugs e.g. sulfonamides (e.g. co-trimoxazole), sulfasalazine, sulfonylureas

Other causes are:

Risk Factors

  • Male sex
  • Neonate – often the first presentation
  • Mediterranean/African/Middle-Eastern ethnic origin
  • Family history
  • Exposure to factors triggering haemolytic crises (mentioned above)

Example History

A 25-year-old man attends the emergency department with jaundice and fatigue. He has recently been prescribed a course of nitrofurantoin for a urinary tract infection.

Investigations:

Haemoglobin:60 g/L(135 – 180 g/L)
Platelets:200 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):81.0 fL(77.0 – 91.0 fL)
White blood cells (WBC):6.0 x 109/L(5.0 – 12.0 x 109/L)
Reticulocyte count:2.3 %(0.2 – 2.0 %)
Bilirubin:60 µmol/L(<17 µmol/L)
ALT:43 IU/L(10 – 50 IU/L)
AST:35 IU/L(10 – 40 IU/L)
ALP:120 IU/L(30 – 130 IU/L)

Presentation

Features of G6PD deficiency are:

  • Pallor
  • Fatigue
  • Dyspnoea
  • Jaundice – due to bilirubin release from haemolysis
    • G6PD often presents as prolonged jaundice in neonates
  • Dark urine – due to bilirubin release haemolysis
  • Gallstones – due to repeated haemolysis and bilirubin release

Investigations

Overview

  • Full blood count (FBC):
    • Shows normocytic, normochromic anaemia
  • Reticulocyte count:
    • Increased – the bone marrow responds by trying to create new, immature red cells 
  • Blood film:
    • Heinz bodies are seen:
      • These form due to denatured haemoglobin from oxidative stress
      • A way of remembering this is that beans can trigger haemolysis – ‘Heinz beans’
    • Bite cells are seen:
      • Heinz bodies are removed from red blood cells, giving a ‘bitten’ appearance to the cell
  • Urinalysis:
    • May show haemoglobinuria – due to intravascular haemolysis
    • Urine dipstick shows urobilinogen – due to intravascular haemolysis
  • Markers of haemolysis:
    • Bilirubin:
      • Raised – due to haemolysis and haemoglobin breakdown
    • Lactate dehydrogenase (LDH):
      • Elevated, but not specific
    • Haptoglobins:
      • Low – haptoglobins bind to free haemoglobin
  • G6PD assay:
    • Definitive test
    • Should not be performed during an acute haemolytic crisis as this can affect results

Management

All patients

In general, management involves avoiding triggers for haemolytic crises and supportive management during them, considering blood transfusions if necessary.

Patient Advice

  • Patients should have genetic counselling regarding the X-linked nature of G6PD deficiency
  • Patients should avoid triggers such as fava beans and notify doctors of their condition so they are not prescribed any drugs that could precipitate a haemolytic crisis 

Complications

  • Gallstones
  • Kernicterus in neonates

Prognosis

  • If managed effectively, G6PD deficiency does not have a significant impact on life expectancy.

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