Children with phenylketonuria (PKU) follow a diet with very low intakes of natural protein, which is devoid of food sources of the omega-3 docosahexaenoic acid (DHA). A resulting DHA depletion has been demonstrated in PKU children and may account for detectable subtle neurological deficits that are not explained by variation in plasma phenylalanine concentrations. We supplemented 36 children with PKU ages 1 to 11 years for 3 months with encapsulated fish oil providing a daily dose of 15 mg DHA/kg body weight. DHA supplementation resulted in significantly faster visual evoked potential latencies, indicating more rapid central nervous system information processing. In addition, DHA significantly improved outcomes in a test of motor function and coordination. No changes over time were seen in age-matched healthy controls. Because the PKU children had a good supply of the omega-3 precursor alpha-linolenic acid, these observations lead us to conclude that endogenous conversion of alpha-linolenic acid is not sufficient to provide adequate amounts of DHA that support optimal function, and hence DHA appears to be a conditional essential substrate for children with PKU. Because early treated PKU children are healthy, with normal fatty acid turnover, these data may indicate a need to supply some DHA to children in general. Further studies are ongoing aiming at establishing quantitative DHA requirements in children.

PKU is one of the few genetic diseases that can be controlled by diet.