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Pyruvate Kinase Deficiency

Pyruvate Kinase Deficiency

- Infrequent genetic metabolic disease caused by a deficiency of pyruvate kinase enzyme, characterized by variable degrees of chronic non-spherocytic hemolytic anemia, leading to clinical manifestations ranging from fatal anemia at birth to fully compensated hemolysis without significant anemia. 

- Pyruvate Kinase (PK): the last enzyme in the glycolytic pathway, catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate and yield adenosine triphosphate (ATP). 


- Red blood cell PK deficiency is caused by mutations in the PKLR gene located on chromosome 1q21. 

- According to reports, there are more than 200 mutations in the PK-LR gene. 

- It is inherited as an autosomal recessive genetic disease. 

- PK is a key regulatory enzyme of glycolysis, the lack of PK leads to two main metabolic abnormalities: Depletion of the ATP and 2,3-diphosphoglycerate (2,3-DPG) content increased. 

- The exact mechanism leading to extravascular hemolysis is unclear, but an important feature is that the spleen selectively sequestrates young red blood cells lacking PK and reticulocytes. 

- Increased levels of 2,3-DPG improve anemia by reducing the oxygen affinity of hemoglobin. 

Clinical Manifestations 

- Commonly neonatal hyperbilirubinemia may require an exchange transfusion. 

- Older children and adults suffer from chronic hemolysis, ranging from mild and compensatory to severe and the need for blood transfusion. 

- Splenomegaly is common. 

- Infection, surgery, and pregnancy can cause acute exacerbations of hemolysis. 

- Parvovirus B19 infection may lead to an aplastic crisis. 


The diagnosis can be considered based on clinical characteristics and laboratory test results:

- Anemia of variable degrees increases unconjugated bilirubin levels and decreases haptoglobin levels.

- Reticulocytosis. 

- Hereditary non-spherocytic hemolytic anemia. 

- Echinocytosis (contracted spiculated cells)

- measuring PK enzymatic activity. Importantly, since enzyme activity is age-dependent on red blood cells, reticulocytosis may mask the lack of PK. 

- Measuring another red blood cell age-specific enzyme, for example, hexokinase might be helpful. 

- Confirmation of the diagnosis requires genetic testing. 

Differential diagnosis 

- Secondary PK deficiency has also been found in blood diseases (acute/chronic leukemia, myelodysplastic syndrome, and sideroblastic anemia). 

- If persistent normal hemolytic anemia, abnormal hemoglobin, and antiglobulin reaction have been ruled out, no spherocytes and normal osmotic fragility, the diagnosis of hereditary nonspherocytic hemolytic anemia should be considered. 


- Neonatal hyperbilirubinemia may require exchange transfusions. 

- Many elderly patients tolerate anemia well and do not require special treatment. 

- Patients with severe hemolysis may require blood transfusion support. 

- Splenectomy can be beneficial in severe cases.

- Daily intake of folic acid to support high red blood cell production: very important for women with EPKD who are planning to become pregnant. 

- Bone marrow transplantation can cure PK deficiency, but it is rarely done. 

- Small molecule activator therapy is nowadays in clinical trials. 


- Iron overload.

- Hyperbilirubinemia.

- Gallstone.

- Splenomegaly 


The prognosis depends on the severity of anemia, but like other chronic hemolytic diseases, gallstones and iron overload may develop, requiring appropriate treatment. 

Pyruvate kinase deficiency is a condition in which red blood cell destruction occurs faster than it should. This can cause anemia (insufficient red blood cells). Most people with pyruvate kinase deficiency lead healthy lives.