Improved identification of heterozygotes for phenylketonuria using blood neopterin and biopterin.

A novel approach that combines information provided by the metabolism of pteridines and that of phenylalanine has been applied to the detection of heterozygotes for phenylketonuria. Phenylalanine, tyrosine, biopterin and neopterin have been measured in serum from normal controls and heterozygotes for classical phenylketonuria, before and after a phenylalanine oral load. Significant differences in neopterin and biopterin mean values in fasting serum and in the mean increase of biopterin induced by the phenylalanine load were found between groups. Inclusion of pteridine data in the discriminant analysis significantly improved the resolution of the classical phenylalanine loading test for the detection of heterozygotes for phenylketonuria.

Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein (a).

Several reports have evaluated the in vitro effect of lipoprotein(a) [Lp(a)] levels on the fibrinolytic system, suggesting that high Lp(a) levels may inhibit fibrinolysis by competing for plasminogen binding in different systems. We have studied plasminogen activation induced by tissue-type plasminogen activator (t-PA), as well as other fibrinolytic parameters, in 25 subjects with Lp(a) levels greater than 30 mg/dl and the results were compared with those found in 23 subjects with Lp(a) less than 30 mg/dl. Both groups were similar in age, sex distribution, living habits and lipid pattern. Plasminogen activation, when measured by t-PA-induced euglobulin clot lysis, was significantly decreased in the group with elevated Lp(a) levels (lysis time, 16.7 +/- 3.3 min) compared with the group with low Lp(a) levels (11.8 +/- 2.0 min), although 8 of the 25 subjects with high Lp(a) levels showed plasminogen activation within the range of the control group. A positive significant correlation between Lp(a) levels and t-PA-induced euglobulin clot lysis time was found. No statistical differences were demonstrated between groups for the other fibrinolytic parameters studied. Addition of purified Lp(a) to the euglobulin fraction or to plasma resulted in a decrease in euglobulin clot lysis. The present study shows that t-PA induced plasminogen activation is decreased in individuals with high circulating levels of Lp(a) supporting the hypothesis that Lp(a) may interfere with the physiological functions of plasminogen.