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| Pyruvate kinase deficiency | |
| Classification and external resources | |
 Phosphoenolpyruvate |
|
| ICD-10 | D55.2 |
|---|---|
| ICD-9 | 282.3 |
| OMIM | 266200 |
| DiseasesDB | 11090 |
| MedlinePlus | 001197 |
| eMedicine | med/1980 |
Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency,[1] is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells.
Both autosomal dominant[2] and recessive[3] 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.
Contents |
Causes
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.
Pathophysiology
Because the ability of erythrocytes to manufacture ATP depends on glycolysis, the cells become deficient in energy and unable to maintain the activity of the basolateral Na+/K+-ATPase. This will result in an increase in intracellular [Na+] which will cause water to diffuse passively into the red blood cell (RBC) and will lead to swelling. This swelling will lead to lysis of the RBCs and an increase in plasma bilirubin. The increase in plasma bilirubin will lead to jaundice and the lysis of the RBCs will lead to hemolytic anemia. 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.
Red blood cells use glycolysis as their sole energy source. In pyruvate kinase deficiency, the last step (phosphoenolpyruvate converted to pyruvate) of glycolsis is unable to occur. A discrepancy between red blood cell energy requirements and ATP generating capacity produces irreversible membrane injury resulting in cellular distortion, rigidity, and lysis. This leads to premature erythrocyte destruction by the spleen and liver.
Treatment
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.
Treatment can include a blood transfusion or removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms.
References
- ^ 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:. ISSN 0361-8609. PMID 6475936.
- ^ Carey, Pj; Chandler, J; Hendrick, A; Reid, Mm; Saunders, Pw; Tinegate, H; Taylor, Pr; West, N (01 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. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11186276.
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