Protein variations associated with Lesch-Nyhan syndrome.

Patients having Lesch--Nyhan syndrome were studied by using enzymatic, immunologic, and two-dimensional electrophoretic techniques. Four hundred proteins were analyzed on each two-dimensional electrophoretogram for positional or quantitative variation. In autoradiograms of lymphocytes stimulated with phytohemagglutinin, there were 11 quantitative differences found in all patients that were significant at the 2P less than 0.01 level. A significant quantitative difference was also found in an analysis of silver-stained gels of unstimulated lymphocytes. Patients had trace amounts of erythrocyte hypoxanthine phosphoribosyl transferase (HPRT) activity and trace or no immunoprecipitable HPRT. However, HPRT was observed in silver-stained erythrocyte electrophoretograms and in autoradiograms from phytohemagglutinin-stimulated lymphocytes. Unstimulated lymphocytes contained 65% of the control HPRT concentration. Currently, the technology of two-dimensional electrophoresis detects a fraction of the total cellular proteins and defective proteins may not show electrophoretic alterations. However, specific secondary changes in other polypeptides may be observed and, when catalogued, will serve as an aid in the diagnosis and understanding of the pathophysiology of metabolic diseases.