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Hereditary deficiency of triosephosphate isomerase in four unrelated families
Insights
Triosephosphate isomerase (TPI) deficiency screening found carriers in 1 in 1000 individuals. Further studies indicate a maximal frequency of 5 in 1000, suggesting TPI deficiency is more common than previously thought.
Area of Science:
- Biochemistry
- Genetics
- Enzymology
Background:
- Triosephosphate isomerase (TPI) is a crucial enzyme in glycolysis.
- TPI deficiency is a rare genetic disorder affecting erythrocytes and leucocytes.
- Previous studies have identified TPI deficiency in a limited number of families.
Purpose of the Study:
- To screen for triosephosphate isomerase deficiency in a large cohort.
- To determine the frequency of TPI deficiency heterozygotes in the population.
- To investigate the clinical and biochemical characteristics of TPI deficiency carriers.
Main Methods:
- Heterozygote screening of 3000 blood samples for triosephosphate isomerase activity.
- Biochemical analysis including enzyme activity assays, metabolite concentrations, and antibody titrations.
- Electrophoretic analysis to detect enzyme variants.
Main Results:
- Triosephosphate isomerase deficiency heterozygotes were identified in three unrelated families.
- Enzyme activity in heterozygotes ranged from 51% to 71% of normal.
- No electrophoretic variants were detected, and other glycolytic enzyme activities were normal.
Conclusions:
- The study indicates a heterozygous frequency of at least 1/1000 for triosephosphate isomerase deficiency.
- The estimated maximal frequency is 5/1000, suggesting the condition is underdiagnosed.
- Routine assaying of this enzyme may improve the detection rate of triosephosphate isomerase deficiency.
Abstract:
Triosephosphate isomerase deficiencies in erythrocytes and leucocytes were discovered in three unrelated families by a heterozygote screening of 3000 blood samples. In addition, a family found by Schroter et al. [not published] was studied. In these four families, only heterozygote carriers were found. In the family described by Freycon et al. with hetero- and homozygote carriers of triosephosphate isomerase deficiency, the heterozygotes were reinvestigated. There was 51% of normal enzyme activity in three of the families. In the other two families the enzyme activity was 64% and 71% of normal. Two of the eleven heterozygotes, both children, were diseased, but it seems unlikely that the disorders resulted from the deficiencies. The activities of thirteen enzymes, the Km of triosephosphate isomerase for glyceraldehyde phosphate and the concentrations of metabolites were normal. Antibody titration showed normal specific activities in four families and 50% of normal in one family. No electrophoretic variant was detected. From the proved heredity, a heterozygous frequency of at least 1/1000 is indicated. A maximal frequency of 5/1000 is estimated by using further instances of triosephosphate isomerase deficiency where heredity has not yet been investigated. An explanation for the small number of known cases is that this enzyme is not routinely assayed.