Conditions · Metabolism (biochemistry)
Pyruvate kinase deficiency !
Pyruvate kinase deficiency is an inherited disease in which red blood cells cannot make enough energy and are destroyed too early.
Updated 2026-10-31
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What it is
Chronic hemolytic anemia due to low activity of red-cell pyruvate kinase (PKLR gene). It is the glycolysis enzyme defect that most often causes hemolysis.
Who gets it
It is rare, but after G6PD deficiency it is the most common enzyme cause of non-spherocytic hemolytic anemia; it is more frequent where parents are related.
Causes
- Autosomal recessive inheritance: two PKLR variants, one from each parent
- Hundreds of variants are known; severity depends on the combination
Risk factors
- Carrier parents or parents related to each other
- Siblings with the disease
Pathophysiology
Without pyruvate kinase the red cell, which has only glycolysis, makes little ATP. It loses its ion pump and flexibility, dehydrates and is removed by the spleen. 2,3-BPG piles up above the block, shifting the hemoglobin curve right and improving oxygen delivery.
Symptoms and signs
- Pallor and tiredness from anemia, mild to severe
- Jaundice (yellow eyes and skin)
- Enlarged spleen (splenomegaly)
- Severe newborn jaundice, which may need an exchange transfusion
- Gallstones at a young age
Diagnosis
- Clinical
- Chronic Coombs-negative hemolytic anemia without spherocytes on the smear and a recessive family pattern.
- Tests
- Blood count with high reticulocytes, raised indirect bilirubin and LDH, low haptoglobin; red-cell pyruvate kinase activity (read with care after a transfusion) and PKLR genetic testing. Ferritin to watch iron.
- Imaging
- Abdominal ultrasound to size the spleen and look for gallstones; MRI to measure iron in the liver.
Treatment
- Medical
- Folic acid and transfusions according to anemia and symptoms
- Medical
- Mitapivat, an oral pyruvate kinase activator, in adults with responsive variants
- Medical
- Iron chelation when iron overload is present
- Surgical
- Splenectomy in heavily transfused cases; cholecystectomy if there are gallstones
Complications
- Iron overload (from hemolysis and transfusions)
- Pigment gallstones
- Thrombosis and severe infections after splenectomy
Prognosis
Highly variable: from mild forms found in adults to severe anemia needing transfusions from childhood.
Test yourself
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Why does pyruvate kinase deficiency mainly affect red cells?
Red cells have no mitochondria: glycolysis is their only ATP source.
How is 2,3-BPG in this deficiency and what does it do?
High: it shifts the hemoglobin curve right and improves oxygen delivery.
How is it inherited?
Autosomal recessive, through PKLR variants.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Pyruvate kinase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); PKLR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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