24th May 2023

Metabolic abnormalities

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

G6PD deficiency is an X-linked recessive inborn error of metabolism. G6PD is required in the metabolic pathway that causes reduction of NADP to NADPH, which is an important cofactor in glutathione metabolism. The main function of this metabolic pathway is to protect RBCs from oxidative stress and injury. Severity of haemolytic anaemia in G6PD deficiency depends on the variant of G6PD that is inherited. It can present as neonatal jaundice in newborns and cause kernicterus.

Clinical features – jaundice, and acute haemolysis precipitated by the following:

• Acute illness
• Drugs (a more comprehensive list can be found on www.g6pd.org)
  • Primaquine, fluoroquinolones, sulfonylureas, chloramphenicol, nitrofurantoin, rasbirucase, isoniazid
• Foods
  • Fava beans, henna compounds

Blood film – Microspherocytes, eccentrocytes (bite cells), blister cells, Heinz bodies, reticulocytes

Treatment – Avoidance of triggering drugs and foods, supportive management in haemolytic crisis

Pyruvate kinase deficiency (PKD)

PKD is a rare, autosomal recessive, inherited red blood cell enzyme disorder resulting in chronic haemolysis. Pyruvate kinase is a key enzyme in the glycolysis pathway. It produces ATP by converting phosphoenolpyruvate to pyruvate. It also modulates NADH production to reduce methaemoglobin levels. In PKD, reduced ATP production decreases RBC deformability (i.e. ability to change shape under applied stress without haemolysing), resulting in RBC damage and mainly extravascular haemolysis.

Clinical features – Neonatal jaundice, anaemia, hepatosplenomegaly secondary to haemolysis, frontal bossing due to extramedullary haemopoiesis

Blood film – normochromic cells, polychromasia, echinocytes (burr cells)

Treatment – Supportive therapy