Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials

Sandesh C S Nagamani, George A. Diaz, William Rhead, Susan A. Berry, Cynthia Le Mons, Uta Lichter-Konecki, James Bartley, Annette Feigenbaum, Andreas Schulze, Nicola Longo, William Berquist, Renata Gallagher, Dennis Bartholomew, Cary O. Harding, Mark S. Korson, Shawn E. McCandless, Wendy Smith, Jerry Vockley, David Kronn, Robert ZoriStephen Cederbaum, J. Lawrence Merritt, Derek Wong, Dion F. Coakley, Bruce F. Scharschmidt, Klara Dickinson, Miguel Marino, Brendan H. Lee, Masoud Mokhtarani

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes. Methods: Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB). Results: After 3. months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p < 0.0001), the number of symptoms per patient (2.5 vs. 1.1; p < 0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p < 0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose. Conclusions: The reduction in symptoms following 3. months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalMolecular Genetics and Metabolism
Issue number1-2
StatePublished - Sep 1 2015

Bibliographical note

Funding Information:
The authors gratefully acknowledge and thank the efforts of the study staff who made this study possible, including N. Schrager (Icahn School of Medicine at Mount Sinai), A. Donovan, J. Crawford, Pediatric TRU Staff, K. Defouw, J. Balliet (The Medical College of Wisconsin), M. Keuth, N. O'Donnell (Long Beach Memorial Hospital), M. Hussain, E. Bailey, A. Orton, M. Ambreen (The Hospital for Sick Children, University of Toronto, ON, Canada), C. Bailey, M.J. Dunkley (The University of Utah), J. Perry, V. de Leon, A. Niemi, K. Cusmano (Stanford University), T. Carlson, J. Parker (University of Minnesota), S. Burr (Children's Hospital Colorado), K. Simpson (Children's National Medical Center), K. Regis (Nationwide Children's Hospital), A. Behrend, T. Marrone (Oregon Health & Sciences University), N. Dorrani (University of California, Los Angeles), C. Heggie (Case Western Reserve University), S. Mortenson (Maine Medical Center), S. Deward (Children's Hospital of Pittsburgh), K. Bart, C. Duggan (SNBL), K. Murray, C. Dedomenico (Tufts Medical Center), C. Gross (University of Florida), L. Brody (Seattle Children's Hospital), M. Mullins, S. Carter, A. Tran, J. Stuff, TCH General Clinical Research Center nursing staff (Baylor), Kathy Lisam (Hyperion), as well as the Clinical and Translational Science Awards/General Clinical Research Center Grants (Baylor College of Medicine, M01RR00188; Case Western Reserve University, NIDDK 1K08DK074573; Clinical and Translational Science Institute at Children's National Medical Center NIH/NCRR, UL1RR31988; Medical College of Wisconsin, UL1RR31973; Mount Sinai School of Medicine, UL1RR29887; Oregon Health & Science University, UL1RR24140; Stanford University, UL1RR25744; Tufts University, UL1RR25752; University of California, Los Angeles, UL1RR33176; University of Colorado, UL1RR25780; University of Florida, UL1RR29890; University of Minnesota, UL1RR33183; University of Pittsburgh, NIH UL1TR000005; University of Utah, UL1RR25764; University of Washington,UL1TR000423), the Urea Cycle Disorders Consortium (NIH Grant U54RR019453) and grants from the O'Malley Foundation, Kettering Fund, and Rotenberg Fund which provided support. SCS Nagamani is an awardee of the National Urea Cycle Disorders Foundation Research Fellowship and is supported by the Clinical Scientist Development Award by the Doris Duke Charitable Foundation. Appendix A

Publisher Copyright:
© 2015 Elsevier Inc..


  • Ammonia
  • Glycerol phenylbutyrate
  • Health-related quality of life
  • Patient-reported outcomes
  • Sodium phenylbutyrate
  • Treatment-related symptoms


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