- Pyruvate kinase deficiency
Name = PAGENAME
DiseasesDB = 11090
ICD10 = ICD10|D|55|2|d|55
ICD9 = ICD9|282.3
OMIM = 266200
MedlinePlus = 001197
eMedicineSubj = med
eMedicineTopic = 1980
Pyruvate kinase deficiency, also called erythrocyte piruvate kinase deficiency, [OMIM|266200] is an
inherited metabolic disorderof the enzyme pyruvate kinasewhich affects the survival of red blood cells.
dominant[cite journal |pmid=6475936 |year=1984 |month=Oct |author=Etiemble, J; Picat, C; Dhermy, D; Buc, Ha; Morin, M; Boivin, P |title=Erythrocytic pyruvate kinase deficiency and hemolytic anemia inherited as a dominant trait |volume=17 |issue=3 |pages=251–60 |issn=0361-8609 |journal=American journal of hematology] and recessive[cite journal |pmid=11186276 |year=2000 |month=Dec |author=Carey, Pj; Chandler, J; Hendrick, A; Reid, Mm; Saunders, Pw; Tinegate, H; Taylor, Pr; West, N |title=Prevalence of pyruvate kinase deficiency in northern European population in the north of England. Northern Region Haematologists Group |volume=96 |issue=12 |pages=4005–6 |issn=0006-4971 |journal=Blood |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11186276 |format=Free full text] inheritance have been observed with thedisorder.
Pyruvate kinase deficiency is the second most common cause of enzyme-deficient
hemolytic anemia, following G6PD deficiency.
A variety of mutations can lead to lowered production, activity, or stability of pyruvate kinase, an
enzymeessential to glycolysis. A total lack of this enzyme's activity will be lethal.
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 jaundiceand 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 hemoglobinoxygen 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.
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 transfusionor removal of the spleen. Treatment is usually effective in reducing the severity of the symptoms.
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