What is pyruvate kinase deficiency?

What is pyruvate kinase deficiency?

Pyruvate kinase deficiency is an inherited lack of the enzyme pyruvate kinase, which is used by red blood cells. Without this enzyme, red blood cells break down too easily, resulting in a low level of these cells (hemolytic anemia).

Why does pyruvate kinase deficiency occur?

Pyruvate kinase deficiency is caused by mutations in the PKLR gene. The PKLR gene is active in the liver and in red blood cells, where it provides instructions for making an enzyme called pyruvate kinase. The pyruvate kinase enzyme is involved in a critical energy-producing process known as glycolysis.

What happens when newborn has pyruvate kinase deficiency?

Most newborns with PK deficiency will develop jaundice because of the breakdown of red cells and the inability of their immature livers to conjugate bilirubin. Some affected infants may require phototherapy for hyperbilirubinemia.

Is pyruvate kinase deficiency intravascular or extravascular hemolysis?

PKD manifests with enzyme levels of <25%. [19] Splenic and hepatic capillaries trap defective RBCs. Extravascular hemolysis occurs, causing hepatosplenomegaly. Intravascular hemolysis may also occur, causing hemoglobinuria.

What happens when pyruvate kinase is blocked?

Pyruvate kinase deficiency is a condition in which red blood cells break down faster than they should. This can lead to anemia (not enough red blood cells). Most people with pyruvate kinase deficiency lead a healthy life.

How does pyruvate kinase deficiency affect the body?

Pyruvate kinase enzyme breaks down a chemical compound called adenosine triphosphate (ATP). Because this enzyme is deficient, there is a lack of ATP. This leads to dehydration of red blood cells and abnormal red cell shapes. The altered red blood cell has a shortened lifespan leading to hemolytic anemia.

Why urine is dark in hemolysis?

Symptoms specifically related to hemolysis include jaundice and dark colored urine due to the presence of hemoglobin (hemoglobinuria). When restricted to the morning hemoglobinuria may suggest paroxysmal nocturnal haemoglobinuria.

How does FBP regulate pyruvate kinase?

FBP is a glycolytic intermediate produced from the phosphorylation of fructose 6-phosphate. FBP binds to the allosteric binding site on domain C of pyruvate kinase and changes the conformation of the enzyme, causing the activation of pyruvate kinase activity. Pyruvate kinase is most sensitive to the effects of FBP.

How is pyruvate kinase deficiency diagnosed?

The standard diagnostic test for PKD is to measure the activity of the pyruvate kinase enzyme in red blood cells. Low activity of this enzyme is indictive of the disorder. This test is only run at specialized laboratories; most clinics and hospitals send this test to be run at these specialized centers.