PK deficiency

Pyruvate Kinase Deficiency (PK deficiency) is a rare genetic disorder that affects the red blood cells. It is an inherited metabolic disorder characterized by a deficiency of the enzyme pyruvate kinase, which is crucial for the glycolytic pathway, a major pathway for energy production in cells. This deficiency leads to a form of hemolytic anemia, where red blood cells are destroyed faster than they can be made, causing various symptoms related to anemia and a decreased ability of the blood to carry oxygen.

Causes and Genetics

PK deficiency is caused by mutations in the PKLR gene, which provides instructions for making the pyruvate kinase enzyme. This enzyme is vital for the final step of glycolysis, a process that generates adenosine triphosphate (ATP), the cell's main energy source. The mutations lead to a reduced activity of pyruvate kinase, disrupting the normal energy production in red blood cells and making them more susceptible to damage and premature destruction. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms

Symptoms of PK deficiency can vary widely among individuals, ranging from mild to severe. Common symptoms include:

• Fatigue and weakness due to anemia
• Jaundice (yellowing of the skin and eyes)
• An enlarged spleen (splenomegaly)
• Gallstones
• Increased risk of infections

In severe cases, individuals may experience complications such as osteoporosis (weakening of the bones) and pulmonary hypertension (high blood pressure in the lungs).

Diagnosis

Diagnosis of PK deficiency typically involves a combination of blood tests, including a complete blood count (CBC) to check for anemia, and specific tests to measure the activity of the pyruvate kinase enzyme. Genetic testing can confirm the presence of mutations in the PKLR gene.

Treatment

There is no cure for PK deficiency, but treatment focuses on managing symptoms and preventing complications. Treatment options may include:

• Blood transfusions to manage severe anemia
• Folic acid supplements to support red blood cell production
• Removal of the spleen (splenectomy) in some cases to reduce red blood cell destruction
• Iron chelation therapy to treat iron overload from frequent blood transfusions

Prognosis

The prognosis for individuals with PK deficiency varies. Some individuals may have mild symptoms and require minimal treatment, while others may experience severe complications requiring more intensive management. With appropriate care, most individuals with PK deficiency can lead active lives.

See Also

• Hemolytic anemia
• Metabolic disorder
• Genetic disorder
• Glycolysis