SN1 SHORT NOTE 5M ★ High-yield

Describe the biochemical basis, precipitating factors and features of G6PD deficiency.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Glucose-6-phosphate dehydrogenase (G6PD) deficiency = an X-linked recessive disorder of the rate-limiting enzyme of the HMP shunt, causing episodic haemolysis on oxidative stress.

The commonest enzymopathy in the world — about 400 million people; common in Africa, the Mediterranean, the Middle East and parts of India
Affects males; females are usually carriers, though lyonisation can make some symptomatic

Biochemical Basis

G6PD deficient → ↓ NADPH (the RBC has no other source) → Glutathione reductase cannot regenerate GSH → Oxidative stress unopposed → Haemoglobin oxidised and denatured → HEINZ bodies precipitate on the membrane → Removed by splenic macrophages → bite cells → intravascular and extravascular haemolysis

Precipitating Factors

Category	Examples
Drugs	Primaquine, chloroquine, dapsone, sulphonamides, nitrofurantoin, ciprofloxacin, aspirin (high dose)
Food	Fava beans (favism) — contains divicine and isouramil
Infection	Any acute infection — the commonest trigger in practice
Chemicals	Naphthalene (mothballs), henna
Metabolic	Diabetic ketoacidosis, severe illness

Clinical Variants

Variant	Population	Severity
G6PD B	Normal	—
G6PD A−	African	Mild — only older RBC affected, so haemolysis is self-limiting
G6PD Mediterranean	Mediterranean, Middle East, Indian	Severe — all RBC affected; favism occurs
Chronic non-spherocytic	Rare	Continuous haemolysis

Clinical and Laboratory Features

Acute haemolytic crisis 1–3 days after exposure — pallor, jaundice, dark urine (haemoglobinuria), back pain, fever
Neonatal jaundice — may be severe enough to cause kernicterus
Blood film — bite cells, blister cells, Heinz bodies (supravital stain), polychromasia, reticulocytosis
↑ Indirect bilirubin, ↑ LDH, ↓ haptoglobin
Enzyme assay must be delayed until 2–3 months after a crisis — young reticulocytes have higher enzyme levels and can give a falsely normal result

Applied Aspects

Management is prevention — a written list of drugs and foods to avoid; treat infection promptly; transfusion only in severe crisis
Screen before prescribing primaquine or dapsone, particularly in malaria-endemic areas
Confers protection against falciparum malaria — the reason the gene is so common; another example of balanced polymorphism, like sickle cell trait
Methylene blue is contraindicated for methaemoglobinaemia in these patients, since its action itself requires NADPH

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