Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders

Lindsay C. Burrage, Mahim Jain, Laura Gandolfo, Brendan H. Lee, Mark L. Batshaw, Mendel Tuchman, Marshall L. Summar, Matthias R. Baumgartner, Susan A. Berry, Stephen Cederbaum, George A. Diaz, Annette Feigenbaum, Renata C. Gallagher, Cary O. Harding, Georg Hoffmann, Douglas S. Kerr, Brendan Lee, Uta Lichter-Konecki, Shawn E. McCandless, J. Lawrence MerrittAndreas Schulze, Margretta R. Seashore, Tamar Stricker, Susan Waisbren, Derek Wong, Mark Yudkoff, Sandesh C.S. Nagamani, Urea Cycle Disorders Consortium

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n. =. 553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.

Original languageEnglish (US)
Pages (from-to)131-135
Number of pages5
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - Sep 1 2014

Bibliographical note

Funding Information:
This work was supported by the NIH ( DK92921 to B.L.), Baylor College of Medicine General Clinical Research Center ( RR00188 ), and the BCM Intellectual and Developmental Disabilities Research Center ( HD024064 ) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development . LCB is supported by the ACMG Foundation/Genzyme Biochemical Genetics Fellowship. SCSN is supported by the Clinical Scientist Development Award by the Doris Duke Charitable Foundation.

Funding Information:
This study was made possible by the Urea Cycle Disorders Consortium (UCDC). The UCDC is part of the NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by U54HD061221 through collaboration between the NIH Office of Rare Diseases Research (ORDR) and the National Center for Advancing Translational Science (NCATS), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2014 Elsevier Inc.


  • Branched-chain amino acids
  • Sodium phenylbutyrate
  • Urea cycle disorder


Dive into the research topics of 'Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders'. Together they form a unique fingerprint.

Cite this