Elevated frequency of carriers for triosephosphate isomerase deficiency in newborn infants.

Seven newborns with erythrocyte triosephosphate isomerase (TPI) activity levels consistent with the existence of a "null" allele in heterozygous form were identified among 146 Black infants studied. This allele frequency of 0.024 is ten times the frequency of 0.0024 observed in White newborns (5 heterozygotes/1048 infants). Each carrier infant has one parent with a level of TPI activity expected of a heterozygous deficient (carrier) adult, whereas the other parent has a normal level of TPI activity, as would be expected for an autosomally inherited genetic trait. All probands as well as affected parents, are asymptomatic as anticipated for heterozygotes having 50% of the expected enzymatic activity. The data are consistent with the existence of a "null" allele, designated TPI 1 degree, at the structural locus for TPI, although no immunologic or direct evidence of inactive or altered subunits was obtained. This high allele frequency implies one of every 2000 Black newborns should be homozygous deficient; this is in conflict with the low number of homozygous deficient afflicted individuals which have been actually identified to date.

Characteristics of enzymes of erythrocytes from newborn infants and adults: activity, thermostability, and electrophoretic profile as a function of cell age.

THe level of enzyme activity, the enzyme thermostability profile, and the isozyme electrophoretic pattern were determined in young and old erythrocytes from newborn infants and adults and in samples from adult individuals with increased reticulocyte counts. Cord blood samples had higher levels of enzymatic activity for 12 of the 14 enzymes measured, adenylate kinase and phosphoglucomutase being the exceptions. The largest differences in activity between newborns and adults were for glutamic oxaloacetic transaminase, hexokinase, glucose 6-phosphate dehydrogenase, and glutathione reductase, while glutamic oxaloacetic transaminase and pyruvate kinase showed the largest differences between young and old cells. The levels of activity of glutathione reductase, adenylate kinase, phosphoglucomutase, lactate dehydrogenase, phosphoglycerokinase, and glucose phosphate isomerase in cord blood samples suggest the regulation of expression of these enzymes is different in fetal erythrocytes than in erythrocytes from an adult. Differences in the thermostability profile of enzymes from cells from different sources and/or of different ages were noted for 5 of 9 enzymes. No unique electrophoretically identifiable fetal isozymes were observed, although differences in isozyme distribution and staining intensity associated with cell source and/or cell age were noted for many of the 23 enzymes examined. Many of these differences in enzyme characteristics have the potential to be confused with genetic alterations in enzyme structure and function.

Erythrocyte enzyme deficiencies assessed with a miniature centrifugal analyzer.

Methods for assaying 16 erythrocyte enzymes have been adapted to the miniature centrifugal analyzer. Less than 15 micro L of whole blood is required for all 16 assays. Variation attributable to temporal effects, rotor effects, and random residual error is minor. Initial population studies of blood from adults and cord-blood samples suggest a CV of less than 12% for 12 of the 16 enzymes; thus it should be possible to identify the heterozygous deficient individual. Preliminary data suggest that three such individuals, with enzyme activity (adenylate kinase, pyruvate kinase, phosphoglycerate kinase) about half the expected, have been identified, as well as two individuals deficient in glucose-6-phosphate dehydrogenase.