Pyruvate kinase deficiency
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|Pyruvate kinase deficiency|
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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 cells and causes them to deform into echinocytes ("burr cells") on peripheral blood smears.
A variety of mutations can lead to lowered production, activity, or stability of pyruvate kinase, an enzyme essential to glycolysis. A total lack of this enzyme's activity will be lethal.
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.
The events leading to hemolysis are still not well understood, but it seems that the lack of ATP impairs the Na+/K+-ATPase and other ATP-dependent processes, leading to a cellular loss of K+ and water and an intracellular accumulation of Na+. This cellular swelling is comparable to ischemic changes in which cells denied of O2 suffer from an ATP deficiency. This swelling causes rigidity of the RBC and eventually splenic hemolysis from an inability to distort through splenic sinusoids. 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 buildup of reaction intermediates can also increase the level of 2,3-bisphosphoglycerate (2,3 BPG) in the cells and affect tissue oxygenation. This will cause a "right shift" in the hemoglobin oxygen saturation curve, implying a decreased oxygen affinity for the hemoglobin and earlier oxygen unloading than under normal conditions. As a result, individuals with pyruvate kinase deficiency may have a greater capacity for physical activity than others with similarly low hemoglobin levels.
Most affected individuals 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 and times of physiologic stress or infection.
- Online 'Mendelian Inheritance in Man' (OMIM) 266200
- Etiemble, J; Picat, C; Dhermy, D; Buc, Ha; Morin, M; Boivin, P (October 1984). "Erythrocytic pyruvate kinase deficiency and hemolytic anemia inherited as a dominant trait". American journal of hematology 17 (3): 251–60. doi:10.1002/ajh.2830170305. ISSN 0361-8609. PMID 6475936.
- Carey, Pj; Chandler, J; Hendrick, A; Reid, Mm; Saunders, Pw; Tinegate, H; Taylor, Pr; West, N (1 December 2000). "Prevalence of pyruvate kinase deficiency in northern European population in the north of England. Northern Region Haematologists Group" (Free full text). Blood 96 (12): 4005–6. ISSN 0006-4971. PMID 11186276.
- Bailliere's Clinical Haematology, Vol. 13, No. 1, pp. 57±81, 2000