Pyruvate Kinase Deficiency

What is pyruvate kinase deficiency?

Pyruvate kinase deficiency (PKD) is a genetic blood disorder. The disease affects red blood cells (RBCs), which carry oxygen throughout the body. People with PKD have low levels of an enzyme called pyruvate kinase in their RBCs. Without this enzyme, red blood cells cannot maintain their structure and break down faster than normal red blood cells, leading to lower numbers of red blood cells (anemia).

What are the symptoms of pyruvate kinase deficiency?

The symptoms of PKD can include pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness, and a rapid heart rate (tachycardia). PKD is caused by a mutation in the PKLR gene, which provides instructions for making the pyruvate kinase enzyme.

How do we treat pyruvate kinase deficiency at Stanford Children’s Health?

There is no cure for PKD at this time. Individuals with a severe case of PKD may require frequent blood transfusions. Chronic blood transfusions are associated with the risks of iron overload, exposure to hepatitis B/C, and can lead to a poor quality of life.

Stanford doctors and researchers are currently evaluating the safety and effectiveness of the drug AMG348 (Mitapivat), which tells the body to produce more of the pyruvate kinase enzyme, in a clinical trial.

At Stanford, we have initiated a clinical trial of gene therapy to treat PKD. Gene therapy involves inserting a normal PKLR gene into a patient’s own blood precursor cells and transplanting those cells back into the patient. We are determining the safety and efficacy of gene therapy for PKD in a clinical trial.

Stem cell transplantation is not routinely used to treat PKD.