Which are the causes of Pyruvate Kinase Deficiency?

Pyruvate Kinase Deficiency (PKD) is a rare genetic disorder that affects the enzyme pyruvate kinase, which plays a crucial role in the energy production process within red blood cells. This deficiency leads to a reduced ability to generate ATP (adenosine triphosphate), the molecule responsible for providing energy to cells. As a result, affected individuals may experience a range of symptoms, including anemia, jaundice, fatigue, and enlargement of the spleen.

There are several causes of Pyruvate Kinase Deficiency:

1. Genetic Mutations: The primary cause of PKD is genetic mutations in the PKLR gene, which provides instructions for producing pyruvate kinase. These mutations can disrupt the normal function of the enzyme, leading to its deficiency.



2. Autosomal Recessive Inheritance: PKD is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder. If both parents carry a single copy of the mutated gene, they have a 25% chance of having an affected child with PKD.



3. Genetic Variants: There are various genetic variants of PKD, each resulting from different mutations in the PKLR gene. The severity of the deficiency and the associated symptoms can vary depending on the specific genetic variant inherited.



4. Enzyme Dysfunction: Pyruvate kinase deficiency leads to a reduced activity of the enzyme, impairing the conversion of phosphoenolpyruvate (PEP) to pyruvate. This disruption in the glycolysis pathway affects the energy production process in red blood cells, leading to their premature destruction and the characteristic symptoms of PKD.



5. Environmental Factors: While genetic mutations are the primary cause of PKD, certain environmental factors can exacerbate the symptoms. These factors include infections, certain medications, and exposure to oxidative stressors, which can further compromise the already impaired red blood cells.

It is important to note that the severity of PKD can vary widely among individuals, even within the same family. Some individuals may have mild or no symptoms, while others may experience severe anemia and complications. Early diagnosis through genetic testing and regular monitoring can help manage the condition and improve the quality of life for individuals with PKD.