Pyruvate kinase deficiency

Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. The exercise capacity of patients with muscle phos-phofiaictokinase deficiency is low, particularly on high-carbohydrate diets. By providing an alternative lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased, work capacity is improved. 

Hirono A et al Pyruvate kinase deficiency and other en2y-mopathies of the erythroc T e. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

Fig. 5. Spiculed red blood cells (echinocyte) in peripheral blood smear of a splenectomized patient with pyruvate kinase deficiency.

Fig. 10. Molecular and biochemical abnormalities of homozygous pyruvate kinase deficiency discovered in our laboratory.

B3. Baronciani, L., and Beutler, E., Analysis of pyruvate kinase-deficiency mutations that produce nonspherocytic hemolytic anemia. Proc. Natl. Acad. Sci. U.S.A. 90,4324-4327 (1993). 

B32. Bianchi, P., Zanella, A., Zappoa, M., Vercellati, C., Terragna, C., Baronciani, L., and Sirchia, G., A new point mutation G/A 1168 (Asp390-Asn) in an Italian patient with erythrocyte pyruvate kinase deficiency. Blood 86 (Suppl. 1), 133a (1995). 

K9. Kanno, H., Wei, D. C. C., Miwa, S., Chan, L. C., and Fujii, H., Identification of a 5 -splice site mutation and a missense mutation in homozygous pyruvate kinase deficiency cases found in Hong Kong. Blood 82 (Suppl. 1), 97a (1993). 

K10. Kanno, H., Balias, S. K Miwa, S., Fujii, H and Bowman, H. S., Molecular abnormality of erythrocyte pyruvate kinase deficiency in the Amish. Blood 83,2311-2316 (1994). 

K11. Kanno, H Fujii, H., and Miwa, S Molecular heterogeneity of pyruvate kinase deficiency identified by single strand conformational polymorphism (SSCP) analysis. Blood 84 (Suppl. 1), 13a... 

L2. Lakomek, M Huppke, P Neubauer, B Pekrun, A., Winkler, H., and Schroter, W., Mutations in the R-type pyruvate kinase gene and altered enzyme kinetic properties in patients with hemolytic anemia due to pyruvate kinase deficiency. Ann. Hematol. 68,253-260 (1994). 

M27. Miwa, S Kanno, H and Fujii, H Concise review Pyruvate kinase deficiency Historical perspective and recent progress of molecular genetics. Am. J. Hematol. 42,31-35 (1993). 

M29. Morimoto, M., Kanno, H., Asai, H., Tsujimura, T., Fujii, H., Moriyama, Y., Kasugai, T., Hirono, A., Ohba, Y Miwa, S., and Kitamura, Y., Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without irradiation. Blood 86,4323-4330 (1995). 

N5. Neubauer, B., Lakomek, M., Winkler, H., Parke, M., Hofferbert, S., Schroter, W., Point mutations in the L-type pyruvate kinase gene of two children with hemolytic anemia caused by pyruvate kinase deficiency. Blood 77, 1871-1875 (1991). 

H. G. Holzhtitter, G. Jacobasch, and A. Bisdorff, Mathematical modeling of metabolic pathways affected by an enzyme deficiency. A mathematical model of glycolysis in normal and pyruvate kinase deficient red blood cells. Eur. J. Biochem. 149(1), 101 111 (1985). 

Pyruvate kinase deficiency is the second most common genetic deficiency that causes a hemolytic anemia (glucose 6-phosphate dehydrogenase, G6PDH, is the most common). Characteristics include ... 

The red blood cell has no mitochondria and is totally dependent on anaerobic glycolysis for ATP. In pyruvate kinase deficiency, the decrease in ATP causes the erythrocyte to lose its characteristic biconcave shape and signals its destruction in the spleen. In addition, decreased ion pumping by Na /K -ATPase results in loss of ion balance and causes osmotic fragility, leading to swelling and lysis. 

Pyruvate kinase deficiency affects 1 in 10,000 people and is the most common inherited disorder of... 

The presence of precipitates of oxidized, denatured hemoglobin (Heinz bodies) helps distinguish the hemolytic anemia caused by of G6PD deficiency from that caused by pyruvate kinase deficiency. 

The answer is B. While all of the listed conditions are consistent with lethargy and developmental defects, the lactic acidosis rules out pyruvate kinase deficiency. Thiamine and niacin deficiencies are unlikely due to the lack of effect of vitamin supplementation. Excess pyruvate is the source of the elevated alanine in the serum. The clinical findings are thus consistent with pyruvate carboxylase deficiency, which is associated with severe hypoglycemia due to fasting due to impaired gluconeogenesis. 

The answer is C. Pyruvate kinase deficiency is ruled out by the elevated serum lactate levels. The coma is associated with a fasting hypoglycemia, which is indicative of pyruvate carboxylase deficiency. The elevated citrulline and lysine in the serum are due to a reduction of aspartic acid levels, which are caused by the reduced levels of oxaloacetate, the product of the pymvate carboxylase reaction. 

Pyruvate kinase deficiency The normal, mature erythrocyte lacks mitochondria and is, therefore, completely dependent on glycoly-... 

Effect of pyruvate kinase deficiency Pyruvate kinase deficiency accounts for 95 percent of all inherited defects in glycolytic enzymes. It is restricted to erythrocytes, and causes mild to severe chronic hemolytic anemia. Altered kinetics (for example, increased Km, decreased Vmax, etc.) most often account for the enzyme deficiency. 

Hematological Disorders. Blood related diseases include hereditary spherocytosis, pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency, and hemoglobinopathies, such as thalassemias. 

Min-Oo, G., Fortin, A., Tam, M.F., Nantel, A., Stevenson, M.M. and Cros, P. (2003) Pyruvate kinase deficiency in mice protects against malaria. Nature Genetics 35, 357-362. 

Kendall AG, Charlow GF. Red cell pyruvate kinase deficiency adverse effect of oral contraceptives. Acta Haematol 1977 57(2) 116-20. 

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