Sandesh C S Nagamani1, George A Diaz2, William Rhead3, Susan A Berry4, Cynthia Le Mons5, Uta Lichter-Konecki6, James Bartley7, Annette Feigenbaum8, Andreas Schulze9, Nicola Longo10, William Berquist11, Renata Gallagher12, Dennis Bartholomew13, Cary O Harding14, Mark S Korson15, Shawn E McCandless16, Wendy Smith17, Jerry Vockley18, David Kronn19, Robert Zori20, Stephen Cederbaum21, J Lawrence Merritt22, Derek Wong21, Dion F Coakley23, Bruce F Scharschmidt23, Klara Dickinson24, Miguel Marino14, Brendan H Lee25, Masoud Mokhtarani23. 1. Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA. Electronic address: Nagamani@bcm.edu. 2. Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, Department of Pediatrics, 1428 Madison Avenue, New York, NY 10029, USA. 3. The Medical College of Wisconsin, MS 716, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA. 4. University of Minnesota, 420 Delaware St. SE, MMC 75, Minneapolis, MN 55455, USA. 5. National Urea Cycle Disorders Foundation, 75 S. Grand Ave, Pasadena, CA 91105, USA. 6. Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA. 7. Long Beach Memorial Hospital, 2801 Atlantic Avenue, Long Beach, CA 90806, USA. 8. Rady Children's Hospital, 3020 Children's Way, San Diego, CA 92123, USA. 9. The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada. 10. The University of Utah, Division of Medical Genetics, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA. 11. Stanford University, 750 Welch Road, #116, Palo Alto, CA 94305, USA. 12. UCSF School of Medicine, 550 16th Street, San Francisco, CA 94158, USA. 13. Nationwide Children's Hospital, 545 South 18th Street, TH485, Columbus, OH 43205, USA. 14. Oregon Health & Science University, 3181 SW Sam Jackson Park Road, A036/B198, Mail code L103, Portland, OR 97239, USA. 15. Tufts Medical Center, Floating Building, 3rd Floor, 800 Washington Street, Boston, MA 02111, USA. 16. Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA. 17. Maine Medical Center, 1577 Congress Street, 2nd Floor, Portland, ME 04102, USA. 18. Children's Hospital of Pittsburgh, One Children's Hospital Drive, 4401 Penn Avenue, Rangos Floor 5, Pittsburgh, PA 15224, USA. 19. Westchester Medical Center, 503 Grasslands Road, Valhalla, NY 10595, USA. 20. University of Florida, UFHSC Box 100296, Gainesville, FL 32610, USA. 21. University of California, Los Angeles, 10833 Le Conte Avenue CHS 32-225, Los Angeles, CA 90095, USA. 22. Seattle Children's Hospital, 4800 Sand Point Way NE M/S W-65945, Seattle, WA 98105, USA. 23. Horizon Therapeutics Inc., 2000 Sierra Point Parkway Suite 400, Brisbane, CA 94005, USA. 24. Anthera Pharmaceuticals, 25801 Industrial Blvd. Suite B, Hayward, CA 94545, USA. 25. Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA.
Abstract
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.
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.
Authors: Uta Lichter-Konecki; G A Diaz; J L Merritt; A Feigenbaum; C Jomphe; J F Marier; M Beliveau; J Mauney; K Dickinson; A Martinez; M Mokhtarani; B Scharschmidt; W Rhead Journal: Mol Genet Metab Date: 2011-05-05 Impact factor: 4.797
Authors: Brendan Lee; William Rhead; George A Diaz; Bruce F Scharschmidt; Asad Mian; Oleg Shchelochkov; J F Marier; Martin Beliveau; Joseph Mauney; Klara Dickinson; Antonia Martinez; Sharron Gargosky; Masoud Mokhtarani; Susan A Berry Journal: Mol Genet Metab Date: 2010-03-23 Impact factor: 4.797
Authors: Wendy Smith; George A Diaz; Uta Lichter-Konecki; Susan A Berry; Cary O Harding; Shawn E McCandless; Cindy LeMons; Joe Mauney; Klara Dickinson; Dion F Coakley; Tristen Moors; Masoud Mokhtarani; Bruce F Scharschmidt; Brendan Lee Journal: J Pediatr Date: 2013-01-13 Impact factor: 4.406
Authors: George A Diaz; Lauren S Krivitzky; Masoud Mokhtarani; William Rhead; James Bartley; Annette Feigenbaum; Nicola Longo; William Berquist; Susan A Berry; Renata Gallagher; Uta Lichter-Konecki; Dennis Bartholomew; Cary O Harding; Stephen Cederbaum; Shawn E McCandless; Wendy Smith; Gerald Vockley; Stephen A Bart; Mark S Korson; David Kronn; Roberto Zori; J Lawrence Merritt; Sandesh C S Nagamani; Joseph Mauney; Cynthia Lemons; Klara Dickinson; Tristen L Moors; Dion F Coakley; Bruce F Scharschmidt; Brendan Lee Journal: Hepatology Date: 2013-01-03 Impact factor: 17.425
Authors: M L Batshaw; S Brusilow; L Waber; W Blom; A M Brubakk; B K Burton; H M Cann; D Kerr; P Mamunes; R Matalon; D Myerberg; I A Schafer Journal: N Engl J Med Date: 1982-06-10 Impact factor: 91.245
Authors: Susan A Berry; Uta Lichter-Konecki; George A Diaz; Shawn E McCandless; William Rhead; Wendy Smith; Cynthia Lemons; Sandesh C S Nagamani; Dion F Coakley; Masoud Mokhtarani; Bruce F Scharschmidt; Brendan Lee Journal: Mol Genet Metab Date: 2014-02-21 Impact factor: 4.797
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Authors: Elena Martín-Hernández; Pilar Quijada-Fraile; Patricia Correcher; Silvia Meavilla; Paula Sánchez-Pintos; Javier de Las Heras Montero; Javier Blasco-Alonso; Lucy Dougherty; Ana Marquez; Luis Peña-Quintana; Elvira Cañedo; María Concepción García-Jimenez; Pedro Juan Moreno Lozano; Mercedes Murray Hurtado; María Camprodon Gómez; Delia Barrio-Carreras; Mariela de Los Santos; Mireia Del Toro; María L Couce; Isidro Vitoria Miñana; Montserrat Morales Conejo; Marcello Bellusci Journal: J Clin Med Date: 2022-08-28 Impact factor: 4.964