Pyruvate Kinase deficiency
⚡ Pyruvate kinase (PK) deficiency results in reduced ATP production within red blood cells (RBCs).
🧪 This leads to high levels of 2,3-DPG, which disrupts the pentose phosphate pathway, ultimately causing premature haemolysis of RBCs.
ℹ️ About
- 🧬 Pyruvate kinase deficiency is an inherited autosomal recessive condition affecting RBCs.
- ⚡ Deficient ATP production shortens RBC lifespan → chronic haemolytic anaemia.
- 🩸 Classified as a congenital non-spherocytic haemolytic anaemia.
Epidemiology
- 👨👩👧 Autosomal recessive inheritance pattern.
- 🔑 Patients are homozygous or compound heterozygotes for PKLR gene mutations.
🧬 Aetiology
- 🧪 Pyruvate kinase is essential in glycolysis, converting phosphoenolpyruvate (PEP) → pyruvate and generating ATP.
- ❌ Mutations in the PKLR gene reduce enzyme activity → inadequate ATP production in RBCs.
- 💔 Without ATP, RBCs lose flexibility → fragile cells removed by the spleen (extravascular haemolysis).
- 📉 High 2,3-DPG shifts O₂ dissociation curve right → easier oxygen release but worsens RBC instability.
🩺 Clinical Features
- 🔄 Variable: from severe neonatal haemolysis to mild anaemia detected in adulthood.
- 🟡 Pallor, jaundice, fatigue, splenomegaly, and pigment gallstones.
- 👶 Neonates: severe jaundice, anaemia, sometimes requiring exchange transfusions.
- 🦠 Aplastic crises may occur with Parvovirus B19 → sudden severe anaemia.
🔎 Investigations
- 🔬 Blood film: “prickle cells” (spiculated red cells).
- 📉 Low haemoglobin (anaemia, severity variable).
- 📈 Reticulocytosis, raised LDH, raised bilirubin.
- ⬇️ Low haptoglobin (consumed in haemolysis).
- 🧪 DAT/Coombs test negative (non-immune haemolysis).
- ✅ Confirmed by measuring reduced RBC pyruvate kinase activity.
⚠️ Complications
- 💎 Pigment gallstones (from chronic haemolysis).
- 🦠 Aplastic crises with viral infections (e.g. Parvovirus B19).
- ⚖️ Iron overload from repeated transfusions.
💊 Management
- 🩺 Depends on severity:
- 💉 Supportive transfusions for severe anaemia (esp. during crises).
- 🌱 Daily folic acid (5 mg) to aid erythropoiesis.
- ✂️ Splenectomy considered in severe haemolysis/high transfusion needs (reduces RBC destruction).
- 🦠 During aplastic crises → intensive transfusion support + monitoring.
- 🧲 Iron chelation if frequent transfusions cause overload.
Cases - Pyruvate Kinase Deficiency
- Case 1 - Neonatal jaundice 👶: A 3-day-old boy develops severe jaundice and anaemia. Family history: cousin required neonatal exchange transfusion. Bloods: unconjugated hyperbilirubinaemia, reticulocytosis, negative Coombs test. Peripheral smear: echinocytes (burr cells). Diagnosis: congenital PK deficiency causing haemolytic anaemia. Managed with phototherapy, transfusion support, and monitoring for kernicterus.
- Case 2 - Chronic haemolysis in childhood 🧒: A 7-year-old girl presents with pallor, fatigue, and intermittent scleral icterus. Splenomegaly noted on exam. FBC: Hb 8.2 g/dL, reticulocytes high. Iron studies: raised ferritin (from chronic transfusions). Diagnosis: PK deficiency with chronic non-spherocytic haemolytic anaemia. Managed with folate supplementation, occasional transfusions, and splenectomy consideration.
- Case 3 - Adult presentation with gallstones 💎: A 28-year-old man with lifelong mild anaemia presents with right upper quadrant pain. Ultrasound: gallstones. Bloods: Hb 10.5 g/dL, raised indirect bilirubin. Peripheral smear: echinocytes. Diagnosis: PK deficiency with pigment gallstones secondary to chronic haemolysis. Managed with cholecystectomy and supportive haematology follow-up.
Teaching Point 🩺: Pyruvate kinase deficiency is a rare autosomal recessive cause of chronic non-spherocytic haemolytic anaemia. Red cells cannot generate enough ATP → membrane instability → haemolysis. Features: neonatal jaundice, chronic anaemia, splenomegaly, gallstones, iron overload. Management: folate, transfusions, splenectomy, iron chelation.
