Pyruvate kinase deficiency
|Pyruvate kinase deficiency|
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|Patient UK||Pyruvate kinase deficiency|
Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency, is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cellsBoth autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.[medical citation needed]
Pyruvate kinase deficiency is due to mutation in PKLR gene, which makes enzyme pyruvate kinase. This enzyme is important in glycolysis, this in turn causes a lesser amount of ATP in red blood cells.
The pathophysiology of pyruvate kinase deficiency has erythrocytes manufacture ATP through glycolysis. A deficiency in pyruvate kinase, the enzyme that potentiates the last step of glycolysis (phosphoenolpyruvate converted to pyruvate), results in red blood cells (RBCs) with decreased energy. Because red blood cells cannot synthesize ATP, cellular death occurs, this is called a 'dehydration at cellular level'. Due to the unavailability of adequate ATP,all active processes in the red blood cell comes to a halt. Sodium potassium ATPase pumps are the first to stop, since the cell membrane is more permeable to potassium than sodium, potassium leaks out. Inter cellular fluid becomes hypertonic, water moves down its concentration gradient out of the cells. Finally cells shrink and die, the mechanism of how distorted red blood cells are destroyed in the spleen is not understood . Partial splenectomies are sometimes performed as a treatment for anemias due to an underlying inability for RBC deformation (hereditary spherocytosis and pyruvate kinase deficiency). This is usually reserved for severe transfusion-dependent anemias as removal of the spleen confers a susceptibility to encapsulated organisms.
The diagnosis of pyruvate kinase deficiency includes a full blood count( differential blood counts) and reticulocyte counts. Tests to determine bile salts (bilirubin) are used to see whether the gall bladder has been compromised.
Most affected individuals with pyruvate kinase deficiency do not require treatment. Individuals who are most severely affected may die in utero of anemia (or may require blood transfusions or splenectomy), but most of the symptomatology is limited to early life of physiologic stress or infection.Treatment can include a blood transfusion or removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms.
- Online 'Mendelian Inheritance in Man' (OMIM) 266200
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