TRIOSEPHOSPHATE ISOMERASE DEFICIENCY - BIOCHEMICAL AND MOLECULAR-GENETIC ANALYSIS FOR PRENATAL-DIAGNOSIS

Inherited deficiency of the glycolytic enzyme triosephosphate isomeras e leads to a multisystem disorder characterized by progressive neuromu scular dysfunction, chronic nonspherocytic hemolytic anemia and increa sed susceptibility to severe infections. Most patients die within the first 6 years. We examined a family with severe triosephosphate isomer ase deficiency. The 1-year-old index patient suffered from hemolytic a nemia, neuromuscular impairment and pneumonias, with the necessity of intermittent mechanical ventilation. Triosephosphate isomerase activit y in erythrocytes was reduced to about 20% of normal. Heat stability o f the enzyme was strongly reduced; concentration of the physiological substrate, dihydroxyacetone phosphate was increased 20-fold due to the metabolic block. Direct sequencing of the triosephosphate isomerase g ene revealed homozygosity for the formerly described GAG-->GAC-mutatio n changing 104 Glu-->Asp. During a 2nd pregnancy we examined a cord bl ood sample obtained in the 19th gestational week. The biochemical data on enzyme activity, heat stability of the enzyme and concentration of dihydroxyacetone phosphate were in the normal range. The molecular ge netic analysis confirmed the presence of the normal triosephosphate is omerase alleles. Pregnancy was continued, resulting in the delivery of an unaffected, healthy newborn.