Erythrocytic pyruvate kinase deficiency and hemolytic anemia inherited as a dominant trait.
A nonspherocytic hemolytic anemia, associated with a pyruvate kinase (PK) deficiency apparently inherited as a dominant trait has been identified in a family. In the affected members, the residual PK activities were 20% that of normal controls, an unusually low level for heterozygous subjects. The anemia was mild except in the proband, a 2-year-old boy who suffered from a severe anemia. The PKs of the proband and of his both parents have been characterized as kinetically and electrophoretically normal enzymes. Immunoprecipitation tests indicated a large amount of L-type inactive protein in the proband and his father. Moreover, an M2 type PK was present in the father's hemolysate, suggesting the existence of a compensatory process that derepressed the corresponding structural gene. We suggest that the presence of one or more mutated subunits in the tetrameric forms of L-type PK leads to the inactivation of these tetramers. This hypothesis accounts for the low residual activity in affected heterozygous members of this family. The severity of the hematological symptoms in the proband, in comparison with the mild hemolysis observed in the other heterozygous members of the family points to the existence of a large spectrum of pathologic expression for an identical PK defect present in a family.
D000328:Adult; D000743:Anemia, Hemolytic / Q000235:genetics*; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000097:blood; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification; D011770:Pyruvate Kinase / Q000097:blood / Q000172:deficiency*
D008565:Membrane Proteins; D011770:Pyruvate Kinase