The Lesch-Nyhan syndrome is characterized clinically by choreoathetosis, 
spasticity, selfmutilation, and mental and growth retardation. Biochemically, 
there is a striking reduction of hypoxanthine-guanine phosphoribosyltransferase 
(HGPRT) activity in affected individuals. We have examined erythrocytes from 14 
patients with the Lesch-Nyhan syndrome for the presence of hypoxanthine-guanine 
phosphoribosyltransferase activity and enzyme protein. In contrast to the usual 
finding of no detectable hypoxanthine-guanine phosphoribosyltransferase 
activity, we have found low levels (0.002-0.79 nmoles/mg protein per hr) of 
hypoxanthine-guanine phosphoribosyltransferase activity in erythrocyte lysates 
from five of these patients. In three of the five patients, hypoxanthine-guanine 
phosphoribosyltransferase activity appeared to be substantially more labile in 
vivo than normal using erythrocytes which had been separated according to their 
density (age). Immunochemical studies using a monospecific antiserum prepared 
from a homogeneous preparation of normal human erythrocyte hypoxanthine-guanine 
phosphoribosyltransferase revealed immunoreactive protein (CRM) in hemolysate 
from all 14 patients with the Lesch-Nyhan syndrome. The immunoreactive protein 
from each patient gave a reaction of complete identity with normal erythrocyte 
hypoxanthine-guanine phosphoribosyltransferase and was present in quantities 
equal to those observed in normal erythrocytes. In addition, a constant amount 
of CRM was found in erythrocytes of increasing density (age) from patients with 
the Lesch-Nyhan syndrome despite the decreasing hypoxanthine-guanine 
phosphoribosyltransferase activity. These studies confirm previous data which 
indicate that the mutations leading to the Lesch-Nyhan syndrome are usually, if 
not always on the structural gene coding for hypoxanthine-guanine 
phosphoribosyltransferase. In addition, although the mutant proteins appear to 
be present in normal amounts, they are often very labile in vivo with respect to 
enzymatic activity. These observations suggest that therapy directed at 
stabilization or activation of enzyme activity in vivo may be of potential 
benefit.