Journal of Inherited Metabolic Disease

, Volume 30, Issue 2, pp 153–158 | Cite as

Double blind placebo control trial of large neutral amino acids in treatment of PKU: Effect on blood phenylalanine

  • R. MatalonEmail author
  • K. Michals-Matalon
  • G. Bhatia
  • A. B. Burlina
  • A. P. Burlina
  • C. Braga
  • L. Fiori
  • M. Giovannini
  • E. Grechanina
  • P. Novikov
  • J. Grady
  • S. K. Tyring
  • F. Guttler
ICIEM 2006


Large neutral amino acids (LNAA) have been used on a limited number of patients with phenylketonuria (PKU) with the purpose of decreasing the influx of phenylalanine (Phe) to the brain. In an open-label study using LNAA, a surprising decline of blood Phe concentration was found in patients with PKU in metabolic treatment centres in Russia, the Ukraine, and the United States. To validate the data obtained from this trial, a short-term double-blind placebo control study was done using LNAA in patients with PKU, with the participation of three additional metabolic centres – Milan, Padua and Rio de Janeiro. The results of the short trial showed significant lowering of blood Phe concentration by an average of 39% from baseline. The data from the double-blind placebo control are encouraging, establishing proof of principle of the role of orally administered LNAA in lowering blood Phe concentrations in patients with PKU. Long-term studies will be needed to validate the acceptability, efficacy and safety of such treatment.


Phenylketonuria Phenylalanine Hydroxylase Cationic Amino Acid Large Neutral Amino Acid Phenylketonuria Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



blood–brain barrier


large neutral amino acids






valine, isoleucine and leucine


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Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • R. Matalon
    • 1
    Email author
  • K. Michals-Matalon
    • 2
  • G. Bhatia
    • 1
  • A. B. Burlina
    • 3
  • A. P. Burlina
    • 3
  • C. Braga
    • 4
  • L. Fiori
    • 5
  • M. Giovannini
    • 5
  • E. Grechanina
    • 6
  • P. Novikov
    • 7
  • J. Grady
    • 1
  • S. K. Tyring
    • 8
  • F. Guttler
    • 9
  1. 1.Department of PediatricsUniversity of Texas Medical Branch, Children’s HospitalGalvestonUSA
  2. 2.University of HoustonHoustonUSA
  3. 3.Inherited Metabolic Disease Unit and Department of Neuroscience, Neurological ClinicUniversity Hospital of PaduaItaly
  4. 4.Diagnósticos Laboratoriais Especializados and Centro Ambulatorial de Prevenção/APAE-Rio de JaneiroBrazil
  5. 5.Department of PediatricsSan Paolo Hospital, University of MilanItaly
  6. 6.Institute of Clinical GeneticsKharkiv State Medical UniversityKharkivUkraine
  7. 7.Department of Clinical GeneticsInstitute of Pediatrics and Child SurgeryMoscowRussia
  8. 8.University of Texas-Health Science CentreHoustonUSA
  9. 9.Kennedy InstituteGlostrupDenmark

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