Open Access Articles- Top Results for Pyruvate kinase deficiency

Pyruvate kinase deficiency

Pyruvate kinase deficiency
File:Phosphoenolpyruvic acid.svg
Classification and external resources
ICD-10 D55.2
ICD-9 282.3
OMIM 266200
DiseasesDB 11090
MedlinePlus 001197
eMedicine med/1980
NCI Pyruvate kinase deficiency
Patient UK Pyruvate kinase deficiency
File:Red Blood Cell abnormalities.png
Distribution of red blood cell abnormalities worldwide

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 and causes them to deform into echinocytes ("burr cells") on peripheral blood smears.

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.


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[citation needed].


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. cell death is by shrinking. 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 hypotonic. Water moves down it's 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 well. 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. [4]

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.


The lysis of the RBCs leads to hemolytic anemia in the newborn and may cause jaundice from increased bilirubin.


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.

See also


  1. ^ Online 'Mendelian Inheritance in Man' (OMIM) 266200
  2. ^ 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. ISSN 0361-8609. PMID 6475936. doi:10.1002/ajh.2830170305. 
  3. ^ 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. 
  4. ^ Bailliere's Clinical Haematology, Vol. 13, No. 1, pp. 57±81, 2000