title: Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials.
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.
authors: Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA. Electronic address: Nagamani@bcm.edu.
authors: Sandesh C S
authors: SC
authors: Nagamani
authors: Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, Department of Pediatrics, 1428 Madison Avenue, New York, NY 10029, USA.
authors: George A
authors: GA
authors: Diaz
authors: The Medical College of Wisconsin, MS 716, 9000 W. Wisconsin Avenue, Milwaukee, WI 53226, USA.
authors: William
authors: W
authors: Rhead
authors: University of Minnesota, 420 Delaware St. SE, MMC 75, Minneapolis, MN 55455, USA.
authors: Susan A
authors: SA
authors: Berry
authors: National Urea Cycle Disorders Foundation, 75 S. Grand Ave, Pasadena, CA 91105, USA.
authors: Cynthia
authors: C
authors: Le Mons
authors: Drexel University, 3141 Chestnut Street, Philadelphia, PA, 19104, USA.
authors: Uta
authors: U
authors: Lichter-Konecki
authors: Long Beach Memorial Hospital, 2801 Atlantic Avenue, Long Beach, CA 90806, USA.
authors: James
authors: J
authors: Bartley
authors: Rady Children's Hospital, 3020 Children's Way, San Diego, CA 92123, USA.
authors: Annette
authors: A
authors: Feigenbaum
authors: The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada.
authors: Andreas
authors: A
authors: Schulze
authors: The University of Utah, Division of Medical Genetics, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132, USA.
authors: Nicola
authors: N
authors: Longo
authors: Stanford University, 750 Welch Road, #116, Palo Alto, CA 94305, USA.
authors: William
authors: W
authors: Berquist
authors: UCSF School of Medicine, 550 16th Street, San Francisco, CA 94158, USA.
authors: Renata
authors: R
authors: Gallagher
authors: Nationwide Children's Hospital, 545 South 18th Street, TH485, Columbus, OH 43205, USA.
authors: Dennis
authors: D
authors: Bartholomew
authors: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, A036/B198, Mail code L103, Portland, OR 97239, USA.
authors: Cary O
authors: CO
authors: Harding
authors: Tufts Medical Center, Floating Building, 3rd Floor, 800 Washington Street, Boston, MA 02111, USA.
authors: Mark S
authors: MS
authors: Korson
authors: Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
authors: Shawn E
authors: SE
authors: McCandless
authors: Maine Medical Center, 1577 Congress Street, 2nd Floor, Portland, ME 04102, USA.
authors: Wendy
authors: W
authors: Smith
authors: Children's Hospital of Pittsburgh, One Children's Hospital Drive, 4401 Penn Avenue, Rangos Floor 5, Pittsburgh, PA 15224, USA.
authors: Jerry
authors: J
authors: Vockley
authors: Westchester Medical Center, 503 Grasslands Road, Valhalla, NY 10595, USA.
authors: David
authors: D
authors: Kronn
authors: University of Florida, UFHSC Box 100296, Gainesville, FL 32610, USA.
authors: Robert
authors: R
authors: Zori
authors: University of California, Los Angeles, 10833 Le Conte Avenue CHS 32-225, Los Angeles, CA 90095, USA.
authors: Stephen
authors: S
authors: Cederbaum
authors: Seattle Children's Hospital, 4800 Sand Point Way NE M/S W-65945, Seattle, WA 98105, USA.
authors: J Lawrence
authors: JL
authors: Merritt
authors: University of California, Los Angeles, 10833 Le Conte Avenue CHS 32-225, Los Angeles, CA 90095, USA.
authors: Derek
authors: D
authors: Wong
authors: Horizon Therapeutics Inc., 2000 Sierra Point Parkway Suite 400, Brisbane, CA 94005, USA.
authors: Dion F
authors: DF
authors: Coakley
authors: Horizon Therapeutics Inc., 2000 Sierra Point Parkway Suite 400, Brisbane, CA 94005, USA.
authors: Bruce F
authors: BF
authors: Scharschmidt
authors: Anthera Pharmaceuticals, 25801 Industrial Blvd. Suite B, Hayward, CA 94545, USA.
authors: Klara
authors: K
authors: Dickinson
authors: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, A036/B198, Mail code L103, Portland, OR 97239, USA.
authors: Miguel
authors: M
authors: Marino
authors: Baylor College of Medicine, One Baylor Plaza, Room R814, Houston, TX 77030, USA.
authors: Brendan H
authors: BH
authors: Lee
authors: Horizon Therapeutics Inc., 2000 Sierra Point Parkway Suite 400, Brisbane, CA 94005, USA.
authors: Masoud
authors: M
authors: Mokhtarani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000641:Ammonia / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D011788:Quality of Life; D057566:Self Report; D011795:Surveys and Questionnaires; D056806:Urea Cycle Disorders, Inborn / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010654:Phenylbutyrates; D000641:Ammonia; C075773:4-phenylbutyric acid; D005990:Glycerol; C570223:glycerol phenylbutyrate
keywords: Ammonia; Glycerol phenylbutyrate; Health-related quality of life; Patient-reported outcomes; Sodium phenylbutyrate; Treatment-related symptoms