G6PD deficiency and enzymopathies: SAQ

This child has an acute haemolytic crisis of glucose-6-phosphate dehydrogenase deficiency triggered by fava beans. The Mediterranean ancestry, the fava bean exposure, the sudden pallor with dark urine, the severe anaemia with a high reticulocyte count, the negative direct antiglobulin test, and the blood film with bite cells, blister cells and Heinz bodies together make the diagnosis. He needs immediate supportive care, transfusion for his severe anaemia, and definitive trigger-avoidance counselling and family screening. [1][9]

Question 1 (10 marks)

Explain the pathophysiology of this child's haemolysis and outline your immediate management. [1][2]

The mechanism is oxidative haemolysis. G6PD is the first enzyme of the pentose phosphate pathway and generates NADPH, which keeps glutathione in its reduced form; reduced glutathione neutralises the oxidants generated inside the red cell. In G6PD deficiency, the oxidants in fava beans consume the limited NADPH and reduced glutathione faster than they are regenerated, so the defence collapses. The oxidants denature haemoglobin into Heinz bodies, which the spleen pits out to form the bite cells and blister cells on the film, and the damaged membrane lyses, causing the intravascular haemolysis that colours the urine dark. [1]

Immediate management begins with removing the trigger, which here is the fava beans, and assessing airway, breathing and circulation. He is tachycardic and pale with a haemoglobin of 54 g per litre, which is well below the transfusion threshold, so he needs crossmatched leucodepleted packed red cells at 10 to 20 mL per kilogram. Ensure hydration to protect the kidney from haemoglobinuria and give folic acid to support marrow recovery. Monitor the haemoglobin, urine output and renal function, and escalate to intensive care if he develops acute kidney injury or haemodynamic instability. [9]

Question 2 (10 marks)

Discuss the diagnosis, the critical timing pitfall of the enzyme assay, and the long-term management and counselling. [2][6]

The diagnosis is confirmed by a quantitative G6PD enzyme assay on a red cell lysate. The critical pitfall, which applies directly here, is that the assay may read falsely normal during an acute crisis. The enzyme-deficient older red cells lyse first, leaving behind the young reticulocytes that carry the highest enzyme activity, so a normal result during a crisis never excludes the diagnosis. The assay must be repeated two to three months later, once the red cell population has returned to its normal age distribution. In this child the film and clinical picture make the diagnosis secure regardless of the acute assay result. [2]

The long-term management is preventive. The definitive intervention is lifelong trigger avoidance, supported by a written list of the drugs and foods to avoid. Under the 2023 Clinical Pharmacogenetics Implementation Consortium guideline, he must avoid the strong oxidant triggers namely primaquine, tafenoquine, rasburicase, methylene blue and dapsone, and avoid fava beans, naphthalene mothballs and henna. Counsel the family that the inheritance is X-linked, so male siblings and the maternal line are at risk and should be screened. Provide a written trigger-avoidance card and a clear safety-net to return if jaundice, dark urine or pallor recur. [6][5]

Neonatal hyperbilirubinaemia extension

A second prompt applies the same principles to the neonate. A term male neonate of Mediterranean ancestry develops severe unconjugated hyperbilirubinaemia on day three with no obvious oxidant exposure. The bilirubin is 340 micromol per litre. [7]

The key teaching point is that a G6PD-deficient neonate can develop kernicterus at a bilirubin level lower than the standard exchange threshold, because the haemolysis compounds the immature blood-brain barrier and hypoalbuminaemia. The practical consequence is a deliberately lower threshold for intensive phototherapy and exchange transfusion. Plot the bilirubin on an hour-specific nomogram, begin intensive phototherapy at 430 to 490 nanometres with maximal skin exposure, and use exchange transfusion at a lower threshold than usual given the raised neurotoxicity risk. Actively seek early bilirubin encephalopathy in the form of lethargy, hypotonia, poor suck and a high-pitched cry, which is a neurological emergency. Confirm the diagnosis with a G6PD assay, repeated later if the acute result is normal, and counsel the family on trigger avoidance before discharge. [7]