Evaluation of the severity of hypoxanthine-guanine phosphoribosyltransferase deficiency using viable T cells.
Peripheral T cells from 3 Lesch-Nyhan patients, 3 normal subjects, and 3 brothers with hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency but without Lesch-Nyhan syndrome (so-called partial deficiency) have been analyzed. Although these brothers contained HGPRT activities neither in the hemolysates nor in the T cell extracts at levels detectable by the regular radioenzyme assay, the enzyme deficiency had not caused any typical neurological symptoms of the Lesch-Nyhan syndrome. Although the T cells from these brothers were at least 10-fold more resistant to 6-thioguanine than normal T cells, they were more than 30-fold less resistant than the T cells from 3 Lesch-Nyhan patients indicating that there is a clear difference in the severity of the enzyme deficiency between the brothers and the Lesch-Nyhan patients. These data indicate that the long-term T cell culture in the medium containing a purine analog whose toxicity depends on a salvaging enzyme is useful for evaluating the severity of the enzyme deficiency in viable cells.
D000293:Adolescent; D002478:Cells, Cultured; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000097:blood*; D007926:Lesch-Nyhan Syndrome / Q000097:blood; D008297:Male; D013601:T-Lymphocytes / Q000201:enzymology*; D013866:Thioguanine / Q000494:pharmacology
D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine