MONOAMINE OXIDASE ACTIVITY IN NORMAL and LESCH-NYHAN FIBROBLASTS

Monoamine oxidase (MAO) activity was studied in cultured skin fibroblasts from 10 Lesch-Nyhan patients, a Lesch-Nyhan variant and 11 controls matched for age. sex and race. Activity (predominantly type A) was measured in cell homogenates using tryptamine as the substrate. For each line activity varied with the conditions of culture. Activity increased 3-10 fold as cultures went from logarithmic to stationary phase of growth. When cultures were confluent, activity was lowered by frequent feedings or the use of fresh medium and serum. Activity for each line remained fairly stable during successive passages, but rose 3-8 fold as cultures became senescent. When comparing activity between control and Lesch-Nyhan lines, cells were cultured under standardized conditions. The mean value of MAO activity in Lesch-Nyhan lines was approximately one fourth of the mean activity in control lines (P < 0.012), In the control population, the distribution of activity appeared to be bimodal. Activities in the Lesch-Nyhan lines fell completely within the lower portion of the control distribution. Cells from a Lesch-Nyhan patient who lacked several of the neurologic symptoms of the disease (including self-mutilation) had an MAO activity 6 fold greater than the control mean. although his hypoxanthine phosphoribosyltransferase activity was <3% of control levels. It appears that: (1) MAO activity is low in fibroblasts from typical Lesch-Nyhan patients: (2) the severity of neurologic symptoms may be correlated with levels of MAO activity: and (3) some interaction between purine and catecholamine metabolism can affect nerve function.