In the present study,
hypoxanthine phosphoribosyltransferase (
HPRT) has been investigated in fibroblasts of 19 patients from 16 different families with
HPRT deficiency, concerning activity, incorporation of 14C-hypoxanthine, and growth in
8-azaguanine and HAT (
hypoxanthine,
azaserine,
thymidine containing) selection media. According to these data we could classify the patients into 5 groups (patients with classical
Lesch-Nyhan syndrome and patients with
HPRT variants of types A, B, C, D). In 3 groups (patients with classical
Lesch-Nyhan syndrome,
HPRT variants C and D), a correlation of residual
HPRT activity with the incorporation of 14C-hypoxanthine as well as growth in
8-azaguanine and HAT selection was observed. The variant A, from a patient with the classical
Lesch-Nyhan syndrome, exhibited higher
HPRT activity than that from all the other patients with the
Lesch-Nyhan syndrome. However, the values of
hypoxanthine incorporation and growth in selection media were as in the classical syndrome. The cells of variant B were resistant to
azaguanine and grew in HAT selection media in the range of control cells, but had
HPRT residual activities similar to those of variants A and C. For the characterization of the genetic heterogeneity of
HPRT, it seems necessary to study the enzymatic properties in
cell extracts as well as the
purine uptake and proliferation of cells in different selection media.