ABSTRACT: Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndrome using techniques based on continuous infusions of [13C]leucine and, in Lesch-Nyhan subjects, [2H5]phenylalanine. The PKU subjects had various degrees of dietary phenylalanine restriction and plasma phenylalanine levels at the time of study ranged from 450–1540 μmol/L (mean 1106). Plasma phenylalanine in the two hyperphenylalaninemic subjects was 533 and 402 μmol/L. Rates of protein synthesis in all PKU subjects (mean 3.71 g/kg/24 h, range 2.68–5.10, [13C]leu-cine as tracer) were in a range similar to or above control values (mean 2.97, range 2.78–3.22, n = 6), as were rates of protein catabolism (PKU mean 4.23 g/kg/24 h, range 3.15–5.45; controls 3.64, 3.50–3.91). Protein turnover values in hyperphenylalaninemia were also similar to those in controls. With [13C]leucine as tracer, both mean protein synthesis and catabolism values in Lesch-Nyhan subjects (mean 4.80 and 5.64 g/kg/24 h, respectively) were higher than values in control children matched for protein intake (synthesis 4.32 ± 0.74 (SD) and catabolism 4.85 ± 0.57 (g/kg/24 h, n = 5). Similar results were obtained in Lesch-Nyhan subjects using [2H5]phenylalanine as tracer. These results suggest that protein turnover is not decreased in either PKU or Lesch-Nyhan syndrome. This conclusion is inconsistent with the hypothesis that tissue damage in PKU results from impaired protein synthesis. The findings also indicate that growth failure in Lesch-Nyhan syndrome is unlikely to be due to decreased protein synthesis resulting from impaired energy metabolism.
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Thompson, G., Pacy, P., Watts, R. et al. Protein Metabolism in Phenylketonuria and Lesch-Nyhan Syndrome. Pediatr Res 28, 240–246 (1990). https://doi.org/10.1203/00006450-199009000-00019