, Volume 33, Issue 6, pp 671-676,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 26 Oct 2010

Large neutral amino acids in the treatment of PKU: from theory to practice


Notwithstanding the success of the traditional dietary phenylalanine restriction treatment in phenylketonuria (PKU), the use of large neutral amino acid (LNAA) supplementation rather than phenylalanine restriction has been suggested. This treatment modality deserves attention as it might improve cognitive outcome and quality of life in patients with PKU. Following various theories about the pathogenesis of cognitive dysfunction in PKU, LNAA supplementation may have multiple treatment targets: a specific reduction in brain phenylalanine concentrations, a reduction in blood (and consequently brain) phenylalanine concentrations, an increase in brain neurotransmitter concentrations, and an increase in brain essential amino acid concentrations. These treatment targets imply different treatment regimes. This review summarizes the treatment targets and the treatment regimens of LNAA supplementation and discusses the differences in LNAA intake between the classical dietary phenylalanine-restricted diet and several LNAA treatment forms.

Communicated by: Nenad Blau
Presented at the Serono Symposia International Foundation Meeting, “Advances and Challenges in PKU”, January 16–17, 2009, in Barcelona, Spain.