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 journalArticle

25 Scopus citations

Abstract

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
Volume113
Issue number1
DOIs
StatePublished - Sep 1 2014

Keywords

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

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    Burrage, L. C., Jain, M., Gandolfo, L., Lee, B. H., Batshaw, M. L., Tuchman, M., Summar, M. L., Baumgartner, M. R., Berry, S. A., Cederbaum, S., Diaz, G. A., Feigenbaum, A., Gallagher, R. C., Harding, C. O., Hoffmann, G., Kerr, D. S., Lee, B., Lichter-Konecki, U., McCandless, S. E., ... Urea Cycle Disorders Consortium (2014). Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders. Molecular Genetics and Metabolism, 113(1), 131-135. https://doi.org/10.1016/j.ymgme.2014.06.005