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Author Notes:

E-mail address: tddougl@emory.edu

T.D.D., A.M.N., A.M.B., S.T.H., and R.H.S. have studied the concept and design, original drafting of manuscript and follow up revisions, and critical review of the manuscript.

A.M.B., A.M.N., T.D.D., and R.H.S. have prepared the interpretation of data.

T.D.D., A.M.N., and A.M.B. prepared the statistical analysis.

The authors have no relevant financial relationships or conflicts of interest to disclose.


Research Funding:

Atlanta Clinical and Translational Science Institute, Grant/Award Number: UL1TR002378; BioMarin Pharmaceutical, Grant/Award Number: Independent investigator award


  • amino acids
  • dietary protein
  • nutrition
  • phenylketonuria
  • supplementation

Large neutral amino acid status in association with P:T ratio and diet in adult and pediatric patients with phenylketonuria.


Journal Title:

JIMD Reports


Volume 50, Number 1


, Pages 50-59

Type of Work:

Article | Final Publisher PDF


Background: Intake of large neutral amino acids (LNAA) may inhibit phenylalanine (PHE) transport across the blood brain barrier and assist with blood PHE control in patients with phenylketonuria (PKU). We evaluated the interrelationship between LNAA in plasma and diet on Phe:Tyr (P:T) ratio in patients with PKU and the influence of dietary factors on plasma LNAA markers. Methods: Plasma amino acid values and 3-day food record analysis from two studies (34 male/30 female; age 4.6-47 years) were examined. For pediatrics (<18 years) and adults (≥18 years) the relationship between P:T ratio, plasma LNAA, and dietary intake patterns were investigated. Results: Dietary factors influencing P:T ratio included intake of total protein (g/kg), medical food (MF) protein (g/kg, % below Rx), and LNAA (g) in the full cohort (P < .05). Associations were found between plasma valine and other dietary and plasma LNAA in pediatrics (P < .05) and plasma LNAA with dietary LNAA intake in adults (P = .019). Plasma P:T ratio was inversely associated with plasma LNAA concentrations in both age groups (P < .05). Aside from histidine in pediatrics (P = .024), plasma LNAA did not differ by having plasma PHE levels within or above the therapeutic range (120-360 μmol/L). Plasma LNAA in both age groups was similar to reported healthy control values. Conclusion: P:T ratio is significantly tied to dietary LNAA, adherence to MF Rx, and plasma LNAA concentrations. Additionally, P:T ratio and valine may be effective clinical proxies for determining LNAA metabolic balance and LNAA quality of the diet in patients with PKU.

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© 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM. CC BY 4.0

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