G6PD deficiency and enzymopathies: Case

This boy has an acute haemolytic crisis of glucose-6-phosphate dehydrogenase deficiency triggered by fava beans, the classic Mediterranean favism. His ancestry, the fava bean exposure two days earlier, 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 make the diagnosis secure at the bedside. The mild cough is the kind of incidental infection that can also be a trigger, but here the fava beans are the dominant precipitant. [1][10]

Clinical findings and differential

The key findings are the Mediterranean ancestry, the fava bean exposure, the severe anaemia with a reticulocytosis, and the direct-antiglobulin-test-negative intravascular haemolysis. The blood film is the discriminator: bite cells and blister cells with Heinz bodies on supravital staining point to oxidative haemolysis, and the negative direct antiglobulin test rules out immune causes. The differential includes hereditary spherocytosis, which would show spherocytes and a family history of splenectomy or gallstones, autoimmune haemolysis, which would be direct-antiglobulin-test-positive, and pyruvate kinase deficiency, which causes chronic haemolysis without oxidant dependence and without Heinz bodies. None of these fits as well as G6PD deficiency here. [1]

The candidate should synthesise the problem representation aloud: a sudden onset direct-antiglobulin-test-negative intravascular haemolysis in a boy of Mediterranean ancestry after fava beans, until proven otherwise G6PD deficiency. The spleen tip is consistent with the mild splenomegaly that accompanies acute haemolysis. The severity, with a haemoglobin under 70 g per litre, places him in the transfusion category. [1]

Investigations and the assay timing pitfall

The diagnosis is confirmed by a quantitative G6PD enzyme assay on a red cell lysate. The candidate must hold the timing pitfall firmly: the assay may be falsely normal during an acute crisis, because the enzyme-deficient older red cells lyse first and the surviving cells are young reticulocytes rich in enzyme. A normal assay during this crisis would never exclude the diagnosis. The plan is to send the assay now but to treat him as G6PD-deficient regardless, and to repeat the assay two to three months later when the red cell population has returned to its normal age distribution. [2]

Genotyping can identify the specific variant, and a point-of-care quantitative test can be used where available. The urine dipstick in a severe crisis shows blood on the pad with no red cells on microscopy, the signature of haemoglobinuria, and the renal function is checked because haemoglobinuria can cause acute kidney injury. The reticulocyte count, raised already, confirms that the marrow is responding. [2]

Management

The immediate management has four parts. First, remove the trigger, which here means stopping the fava beans and treating the mild viral illness supportively. Second, ensure hydration to protect the kidney from haemoglobinuria, with oral fluids if he tolerates them and intravenous fluids if he does not, aiming for a good urine output. Third, give folic acid to support the marrow recovery. [10]

Fourth, transfuse, because his haemoglobin of 57 g per litre is well below the threshold. The product is crossmatched leucodepleted packed red cells at 10 to 20 mL per kilogram, and he is monitored during and after the transfusion. The indications for paediatric intensive care are acute kidney injury from haemoglobinuria, deepening or uncontrolled haemolysis, and haemodynamic instability. Once the haemoglobin stabilises and he is clinically well and tolerating oral intake, he can be stepped down to the ward and prepared for discharge. [10]

Discharge counselling and follow-up

The discharge plan is the heart of the long case, because the definitive management of G6PD deficiency is preventive. The family receives a written trigger-avoidance list, naming the strong oxidant drugs to avoid under the 2023 Clinical Pharmacogenetics Implementation Consortium guideline: primaquine, tafenoquine, rasburicase, methylene blue, and dapsone, and the foods and chemicals to avoid, namely fava beans, naphthalene mothballs, and henna. The family is taught that the inheritance is X-linked, so male siblings and the maternal line are at risk and should be screened with a quantitative assay. [6]

A written avoidance card is provided for the family to show every future prescriber, and a clear safety-net is given so that the family returns at once if jaundice, dark urine, or pallor recur. The G6PD assay is repeated two to three months later to confirm the diagnosis and the variant. The candidate should close by affirming that the prognosis is excellent with trigger avoidance, that the family should carry the avoidance list at all times, and that the boy can lead a full and normal life between crises. [6][2]