scholarly journals Hereditary nonspherocytic hemolytic anemia and hexokinase deficiency

Blood ◽  
1978 ◽  
Vol 51 (5) ◽  
pp. 935-940 ◽  
Author(s):  
E Beutler ◽  
PG Dyment ◽  
F Matsumoto
Keyword(s):  
Thermal Stability ◽  
Hemolytic Anemia ◽  
Potent Inhibitor ◽  
Glucose Consumption ◽  
Kinetic Properties ◽  
Red Cell ◽  
Hexokinase Activity ◽  
Thermal Stability Of ◽  
Chronic Hemolytic Anemia ◽  
2,3 Dpg

An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.

scholarly journals Hereditary nonspherocytic hemolytic anemia and hexokinase deficiency

Blood ◽  
1978 ◽  
Vol 51 (5) ◽  
pp. 935-940 ◽  
Author(s):  
E Beutler ◽  
PG Dyment ◽  
F Matsumoto
Keyword(s):  
Thermal Stability ◽  
Hemolytic Anemia ◽  
Potent Inhibitor ◽  
Glucose Consumption ◽  
Kinetic Properties ◽  
Red Cell ◽  
Hexokinase Activity ◽  
Thermal Stability Of ◽  
Chronic Hemolytic Anemia ◽  
2,3 Dpg

Abstract An 11-yr-old child with mild chronic hemolytic anemia was found to have decreased red cell hexokinase activity in spite of the reduced mean age of her red cell population. Similar decreases in red cell hexokinase activity were documented in the patient's parents and in one sib. The red cells were morphologically normal. Red cell 2,3-DPG levels were normal and ATP and glucose-6-phosphate levels were diminished. The kinetic properties, electrophoretic mobility, and thermal stability of the residual red cell hexokinase were normal or nearly so. Glucose consumption of the hexokinase-deficient cells was not appreciably decreased, probably because less of the potent inhibitor glucose-6- phosphate was present in the erythrocytes. It is likely, although not certain, that in this patient nonspherocytic hemolytic anemia resulted from hexokinase deficiency.

scholarly journals Hereditary nonspherocytic hemolytic anemia due to a new hexokinase variant with reduced stability

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 690-697 ◽  
Author(s):  
M Magnani ◽  
V Stocchi ◽  
L Cucchiarini ◽  
G Novelli ◽  
S Lodi ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Specific Activity ◽  
Blood Platelets ◽  
Phenotypic Variability ◽  
Ph Dependence ◽  
Glucose Consumption ◽  
Heat Stability ◽  
Normal Activity ◽  
Red Cell ◽  
Hexokinase Activity

A 27-year-old woman with severe chronic hemolytic anemia was found to have reduced red cell hexokinase activity when the degree of reticulocytosis was considered. This enzyme had normal pH-dependent activity, normal Km for glucose, fructose, and mannose, normal Km for Mg adenosine triphosphate (ATP)2- and Ki for glucose-1,6-diphosphate. Furthermore, the pH-dependence and orthophosphate dependence of Ki for glucose-1,6-diphosphate were normal. However, this hexokinase was inactivated rapidly at 44 degrees C. No abnormalities were found in the red cell hexokinase isozymic pattern when it was compared with the profile obtained from cells of similar age. The hexokinase specific activity was reduced in all the red blood cell fractions obtained by density gradient ultracentrifugation; a marked difference in the distribution of cells through the gradient was evident. Among the glycolytic intermediates, a significant decrease of 2,3- diphosphoglycerate was evident. ATP and glucose 6-phosphate were also reduced when compared with cells of similar. Glucose consumption of the hexokinase-deficient cells decreased, but the rate of glucose metabolized through the hexose monophosphate shunt was unchanged. Although the total hexokinase activity in lymphocytes was only reduced by 37%, a marked hexokinase deficiency was detected in blood platelets (20% to 25% of normal activity). The parents and one of two siblings of the patient were heterozygous for the defect, with 66% to 74% of normal erythrocyte hexokinase activity and reduced heat stability of the enzyme. These results, when compared with those obtained in previously reported cases of hexokinase deficiency, provide further evidence of the broad phenotypic variability that characterizes this disorder. Furthermore, it is suggested that failure of energy generation is probably the primary cause of hemolytic anemia in hexokinase deficiency.

scholarly journals Hereditary nonspherocytic hemolytic anemia due to a new hexokinase variant with reduced stability

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 690-697 ◽  
Author(s):  
M Magnani ◽  
V Stocchi ◽  
L Cucchiarini ◽  
G Novelli ◽  
S Lodi ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Specific Activity ◽  
Blood Platelets ◽  
Phenotypic Variability ◽  
Ph Dependence ◽  
Glucose Consumption ◽  
Heat Stability ◽  
Normal Activity ◽  
Red Cell ◽  
Hexokinase Activity

Abstract A 27-year-old woman with severe chronic hemolytic anemia was found to have reduced red cell hexokinase activity when the degree of reticulocytosis was considered. This enzyme had normal pH-dependent activity, normal Km for glucose, fructose, and mannose, normal Km for Mg adenosine triphosphate (ATP)2- and Ki for glucose-1,6-diphosphate. Furthermore, the pH-dependence and orthophosphate dependence of Ki for glucose-1,6-diphosphate were normal. However, this hexokinase was inactivated rapidly at 44 degrees C. No abnormalities were found in the red cell hexokinase isozymic pattern when it was compared with the profile obtained from cells of similar age. The hexokinase specific activity was reduced in all the red blood cell fractions obtained by density gradient ultracentrifugation; a marked difference in the distribution of cells through the gradient was evident. Among the glycolytic intermediates, a significant decrease of 2,3- diphosphoglycerate was evident. ATP and glucose 6-phosphate were also reduced when compared with cells of similar. Glucose consumption of the hexokinase-deficient cells decreased, but the rate of glucose metabolized through the hexose monophosphate shunt was unchanged. Although the total hexokinase activity in lymphocytes was only reduced by 37%, a marked hexokinase deficiency was detected in blood platelets (20% to 25% of normal activity). The parents and one of two siblings of the patient were heterozygous for the defect, with 66% to 74% of normal erythrocyte hexokinase activity and reduced heat stability of the enzyme. These results, when compared with those obtained in previously reported cases of hexokinase deficiency, provide further evidence of the broad phenotypic variability that characterizes this disorder. Furthermore, it is suggested that failure of energy generation is probably the primary cause of hemolytic anemia in hexokinase deficiency.

scholarly journals Erythrocyte Pyruvate Kinase Deficiency in Non-spherocytic Hemolytic Anemia: A System of Multiple Genetic Markers?

Blood ◽  
1968 ◽  
Vol 32 (1) ◽  
pp. 33-48 ◽  
Author(s):  
WOLF W. ZUELZER ◽  
ABNER R. ROBINSON ◽  
THERESA H. J. HSU
Keyword(s):  
Hemolytic Anemia ◽  
Genetic Diagnosis ◽  
Glucose Consumption ◽  
Normal Glucose ◽  
Red Cell Survival ◽  
Severe Type ◽  
Subordinate Role ◽  
Index Cases ◽  
2,3 Dpg

Abstract Extreme intrafamilial differences between PK-deficient phenotypes regarding hemolysis, ATP stability, and glucose consumption were observed in two pedigrees in which the index cases had severe nonspherocytic hemolytic anemia. Genetic analysis was consistent with heterozygosity for two distinct interacting mutants in minimally affected relatives of severely anemic homozygotes. Neither the mature erythrocytes of the former nor the reticulocyte-rich cell populations of the latter showed accumulation of glycolytic intermediates, but 2,3-DPG was elevated in both. Despite severe PK deficiency, red cell survival in the minimal type was near normal, glucose consumption was unaffected in three of four subjects tested, and ATP maintenance in vitro was adequate, in contrast to the severe type in which these parameters were grossly depressed. The genetic and pathophysiologic implications of these findings are discussed. The possibility is considered that defective glycolysis may play a subordinate role in the hemolytic process associated with PK deficiency and that the enzyme defect may be a genetic marker for as yet unknown erythrocytic abnormalities involving an increase of 2,3-DPG and possibly primary membrane lesions creating excessive demands on the energy metabolism of the erythrocytes. Regardless of the mode of gene action, it is concluded that the nonspherocytic hemolytic anemias associated with PK deficiency are genetically and phenotypically heterogeneous, and that the genetic diagnosis cannot rest on PK assay alone.

scholarly journals Normal and Variant Isoenzymes of Human Blood Cell Hexokinase and the Isoenzyme Patterns in Hemolytic Anemia

Blood ◽  
1970 ◽  
Vol 36 (2) ◽  
pp. 219-227 ◽  
Author(s):  
CIGDEM ALTAY ◽  
CHESTER A. ALPER ◽  
DAVID G. NATHAN
Keyword(s):  
Hemolytic Anemia ◽  
Cell Metabolism ◽  
Electrophoretic Pattern ◽  
Red Cells ◽  
Red Cell ◽  
Hexokinase Activity ◽  
Individual Bands ◽  
Agarose Electrophoresis ◽  
Human Blood Cell ◽  
Isoenzyme Patterns

Abstract Electrophoresis of red cell hexokinase in agarose electrophoresis revealed two major (1 and 2) and two minor (3 and 4) bands. Platelet and leukocyte hexokinase patterns differed from those of red cells. There was a strong band 1, but considerably faster bands termed 5, 6 and 7 were also observed which were sensitive to changes in glucose concentration. The presence of contaminating leukocytes can significantly alter the electrophoretic pattern of "red cell" hexokinase activity. Bands 2, 3 and 4 of red cells appeared to be synthesized independently of band 1 and absence of band 1 did not effect either red cell metabolism or survival. Absence of bands 2, 3 and 4 may be associated with hemolytic anemia, decreased erythrocyte hexokinase activity and decreased erythrocyte glycolysis. Young red cells had increased activity of all bands, particularly band 2. No influence of hemoglobin type on hexokinase patterns was observed, nor was there any selective influence of cell storage, medium glucose, or 2-mercaptoethanol on individual bands. None of the various isoenzyme patterns were associated with abnormal hexokinase kinetics.

scholarly journals A family with red cell pyrimidine 5'-nucleotidase deficiency

Blood ◽  
1976 ◽  
Vol 47 (6) ◽  
pp. 919-922
Author(s):  
I Ben-Bassat ◽  
F Brok-Simoni ◽  
G Kende ◽  
F Holtzmann ◽  
B Ramot
Keyword(s):  
Hemolytic Anemia ◽  
Peripheral Blood ◽  
Blood Smear ◽  
Peripheral Blood Smear ◽  
Early Infancy ◽  
Red Cell ◽  
Chronic Hemolytic Anemia ◽  
Congenital Hemolytic Anemia

Congenital hemolytic anemia associated with pyrimidine 5′-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis.

scholarly journals Study of a kindred with partial deficiency of red cell 2,3- diphosphoglycerate mutase (2,3-DPGM) and compensated hemolysis

Blood ◽  
1978 ◽  
Vol 51 (6) ◽  
pp. 1107-1116
Author(s):  
SF Travis ◽  
J Martinez ◽  
J Jr Garvin ◽  
J Atwater ◽  
P Gillmer
Keyword(s):  
Lactate Production ◽  
Oxygen Affinity ◽  
Osmotic Fragility ◽  
Glucose Consumption ◽  
Enzyme Synthesis ◽  
Red Cell ◽  
Autosomal Dominant Trait ◽  
The Stability ◽  
Partial Deficiency ◽  
2,3 Dpg

A kindred with partial deficiency of red cell 2,3-diphosphoglycerate mutase (2,3-DPGM) was studied. The propositus presented with indirect hyperbilirubinemia, normal hemoglobin (15.8 g/dl), and elevated reticulocyte count (4.6%). The red cell 51Cr survival was decreased (tau1/2 16 days). Incubated osmotic fragility was normal; autohemolysis was increased and corrected with glucose and ATP. The P50 was 18.5 mm Hg (normal 25.5 +/- 3), but the stability, electrophoresis, and fingerprinting of hemoglobin were normal. The concentration of 2,3- diphosphoglycerate (2,3-DPG) was reduced to 43% of normal. Red cell 2,3- DPGM was decreased to 59% of normal; 2,3-DPG phosphatase was similarly decreased. All red cell glycolytic and hexose monophosphate shunt enzymes, glycolytic intermediates other than 2,3-DPG, and glucose consumption and lactate production were normal. Five family members showed similar hematologic findings. The deficiency appears to be secondary to decreased enzyme synthesis and to be inherited as an autosomal dominant trait in this family. Partial deficiency of 2,3-DPGM should now be considered in the differential diagnosis of compensated hemolysis associated with increased oxygen affinity.

Red cell ektacytometry in two patients with chronic hemolytic anemia and three new α-spectrin variants

2021 ◽  
Author(s):  
Joan-Lluis Vives-Corrons ◽  
Elena Krishnevskaya ◽  
Inés Hernández-Rodriguez ◽  
Salvador Payán-Pernia ◽  
Ángel F. Remacha Sevilla ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Red Cell ◽  
Chronic Hemolytic Anemia

A comparative analysis of the evolutionary patterning and mechanistic bases of lactate dehydrogenase thermal stability in porcelain crabs, genus Petrolisthes

2001 ◽  
Vol 204 (4) ◽  
pp. 767-776
Author(s):  
J.H. Stillman ◽  
G.N. Somero
Keyword(s):  
Thermal Stability ◽  
Comparative Analysis ◽  
Lactate Dehydrogenase ◽  
Protein Interactions ◽  
Kinetic Properties ◽  
Post Translational Modification ◽  
Extrinsic Factors ◽  
Thermal Stability Of ◽  
Interspecific Diversity

The kinetic properties of orthologous homologs (orthologs) of enzymes are typically correlated with environmental temperatures in species adapted to different thermal regimes, but correlations between adaptation temperature and enzyme thermal stability are less clear. Although the thermal stability of a protein is related chiefly to its primary structure (including post-translational modification), thermal stability can also be altered by extrinsic factors present in the intracellular milieu. Here, we present a comparative analysis of the thermal stability of lactate dehydrogenase (LDH) orthologs from 22 congeneric species of porcelain crab (genera Petrolisthes and Allopetrolisthes) from a broad range of thermal habitats. Interspecific diversity of LDH stability is high: temperatures required for a 50 % loss of activity in 10 min ranged from 65 to 75.5 degrees C, corresponding to half-lives of less than 1 min to more than 3 h at 70 degrees C. Although stability is positively correlated with maximal habitat temperature in some sister taxa, phylogenetic comparative analysis incorporating all 22 species does not indicate that the interspecific diversity of LDH stability represents an adaptive response to current thermal habitats. Examination of the mechanistic bases of LDH stabilization indicates that differences in stability are related both to properties of the LDH molecule itself (intrinsic stability) and to the effects of extrinsic protein(s). Intrinsic differences were shown by the unfolding of structure during heating, as measured by circular dichroism spectroscopy. Stabilizing effects of extrinsic proteins are implied by the results of cellular fractionation experiments that removed low-molecular-mass solutes and proteins from the muscle homogenates. We conclude that the overall structural stability and functional properties of proteins can evolve independently and that in vivo protein-protein interactions can provide another means to regulate protein stability selectively.

NONSPHEROCYTIC CONGENITAL HEMOLYTIC ANEMIA DUE TO A NEW G-6-PD VARIANT: G-6-PD ALHAMBRA

PEDIATRICS ◽  
1970 ◽  
Vol 45 (2) ◽  
pp. 230-235
Author(s):  
Ernest Beutler ◽  
Robert Rosen
Keyword(s):  
Thermal Stability ◽  
Hemolytic Anemia ◽  
Red Cells ◽  
Essentially Normal ◽  
New Variant ◽  
Thermal Stability Of ◽  
Congenital Hemolytic Anemia

An 11-year-old boy was first known to have a hemolytic episode at the age of 8 years, and a diagnosis of nonspherocytic congenital hemolytic anemia due to G-6-PD deficiency was made soon after the hemolytic episode. The red cells of the patient contained a level of G-6-PD activity approximating 10 to 25% of normal. The residual enzyme was partly purified and characterized. It proved to be electrophoretically slow, and was kinetically essentially normal. The thermal stability of the enzyme was reduced and its stability in vivo was markedly diminished. This enzyme represents a new variant which has been named G-6-PD Alhambra.

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