Hereditary deficiency of triosephosphate isomerase in four unrelated families

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.

Use of Mathematical Models for Predicting the Metabolic Effect of Large‐Scale Enzyme Activity Alterations

“…Calculated range of disease Properties of deficient enzymes Number of References diseased minimum range of minimum enzyme unstable kinetic change in persons survival chronic normal activity variants change isoenzyme activity disease activity Tanaka, 1990;Valentine, 1983;Board, 1978;Rijksen, 1983;Miwa, 1985;Paglia, 1981;Necheles, 1970Tanka, 1990Paglia, 1974;Zanella, 1980;Neubauer, 1990;Arnold, 1973Tanka, 1990Vora, 1983;Valentine, 1984 ;Fogelfeld, 1990Kishi, 1987Miwa, 1981 ;Valentine, 1984Eber, 1979Valentine, 1984;Rosa, 1985 ;Zanella, 1985Waller, 1974Tanaka, 1990Maeda, 1991 ;Fujii, 1980Fujii, , 1992Valentine, 1984Schroter, 1965Rosa, 1973Rosa, , 1978Buc, 1974;Rosa, 1989;Tanaka, 1990 Syllm- Rapoport, 1965…”

Elevated Frequency of Carriers for Triosephosphate Isomerase Deficiency in Newborn Infants

“…(II,12) indicate that the frequency ofTPI deficient carriers (heterozygous individuals with one normal and one "null" allele) is much higher than expected from the number of reported homozygous deficient individuals. This report will extend the earlier report of Mohrenweiser (23), present the frequency within ethnic groups and examine the basis for the deficiency.…”

Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme.

“…Homozygous-deficient individuals usually have 3-20% of normal TPI activity; all of this activity is heat labile, suggesting that at least one allele encodes a structurally altered protein (3, 9, 10). The other allele is presumably null, since mutations producing no detectable enzyme activity or immunologically cross-reacting material are by far the most prevalent abnormality affecting the human TPI locus (11)(12)(13)(14)(15).In the present study, we have determined the nucleotide sequence of two TPI alleles, each of which was isolated from unrelated individuals homozygous for TPI deficiency. Relative to a normal allele (16), each allele harbors a single base pair change.…”

“…Homozygous-deficient individuals usually have 3-20% of normal TPI activity; all of this activity is heat labile, suggesting that at least one allele encodes a structurally altered protein (3,9,10). The other allele is presumably null, since mutations producing no detectable enzyme activity or immunologically cross-reacting material are by far the most prevalent abnormality affecting the human TPI locus (11)(12)(13)(14)(15).…”