Patients & Caregivers

Pyruvate Kinase Deficiency

What is Pyruvate Kinase Deficiency?

Pyruvate kinase (PK) deficiency is a rare inherited disease that causes a lifelong condition called hemolytic anemia, a certain type of anemia where the body destroys red blood cells, as well as other serious complications. The precise reason for the destruction is not well understood, but it is thought to occur because red blood cell membranes become unstable in people with low levels of the PKR enzyme, the form of pyruvate kinase that is present in red blood cells.

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What causes PK deficiency?

Pyruvate kinase is an enzyme involved in glycolysis: the conversion of sugar, or glucose, into energy and critical for the survival of red blood cells. PKR is the form of pyruvate kinase that is present in red blood cells. Mutations in PKR cause failures in red blood cell glycolysis, which lead to a disease known as pyruvate kinase deficiency, or PK deficiency. PK deficiency results in a shortened lifespan for red blood cells.

Children with PK deficiency have inherited a mutated form of PKR from each of their parents. These children produce a PKR enzyme that has only a fraction of the level of normal enzyme activity. Parents typically do not exhibit any symptoms because each of them has only one copy of the mutated PKR enzyme (compared with affected children who have two copies) and are clinically “normal.”

What are the treatment options for PK deficiency?

Infantile cases might require immediate life-saving intervention via replacement of their entire blood system with a donor’s blood, referred to as an exchange transfusion. Treatment of PK deficiency is supportive, including blood transfusions, splenectomy, chelation therapy to address iron overload and/or interventions for other disease-related morbidity. Currently, there is no approved medicine to address the underlying etiology of life-long hemolytic anemia. If you have been diagnosed with PK deficiency, talk to your doctor to determine the best options for you.

What are the signs and/or symptoms of PK deficiency?

People with PK deficiency can experience a range of signs and symptoms, including:

  • Anemia (not having enough red blood cells to carry sufficient amounts of oxygen throughout the body)
  • Feeling fatigued, tired and/or weak
  • Shortness of breath
  • Exercise intolerance
  • Iron overload (having too much iron in the body) resulting from lifelong (or chronic) hemolytic anemia and as a comorbidity related to transfusions
  • Jaundice (yellow coloring of the skin and eyes)
  • Scleral icterus (yellow coloring of the whites of the eyes)
  • Abdominal pain
  • Enlarged spleen (splenomegaly)
  • Gallstones

How is PK deficiency diagnosed?

A number of laboratory testing methods can be requested by a physician to determine if a person has PK deficiency. Typically, one or both of the following types of tests can be performed:

  • Erythrocyte (red blood cell) PK enzymatic activity (enzyme or biochemical assay)
  • Mutation analysis of the PKLR gene (molecular testing)

What is the impact of PK deficiency?

Similar to other rare genetic diseases, the long-term impact of PK deficiency is not well understood. However, even with the current supportive care, it is clear that there are life-long complications as a result of the disease. Boston Children’s Hospital, in cooperation with Agios, is conducting a natural history study to review the medical records of patients with PK deficiency and follow a group of these patients to understand how the disease progresses and how best to treat it.