Citrulline in the management of patients with urea cycle disorders
Abstract Background Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available reg...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-07-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02800-8 |
| _version_ | 1827894916057923584 |
|---|---|
| author | Apolline Imbard Juliette Bouchereau Jean-Baptiste Arnoux Anaïs Brassier Manuel Schiff Claire-Marine Bérat Clément Pontoizeau Jean-François Benoist Constant Josse François Montestruc Pascale de Lonlay |
| author_facet | Apolline Imbard Juliette Bouchereau Jean-Baptiste Arnoux Anaïs Brassier Manuel Schiff Claire-Marine Bérat Clément Pontoizeau Jean-François Benoist Constant Josse François Montestruc Pascale de Lonlay |
| author_sort | Apolline Imbard |
| collection | DOAJ |
| description | Abstract Background Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies. Data collection included patient background, treatment details, changes in biochemical parameters (plasma ammonia and amino acids concentrations), decompensations, and patient outcomes. Results Overall, 79 patients (median age at diagnosis, 0.9 months) received citrulline and/or arginine in combination with a restricted protein diet, most with ornithine transcarbamylase (n = 57, 73%) or carbamoyl phosphate synthetase 1 (n = 15, 19%) deficiencies. Most patients also received ammonium scavengers. Median follow-up was 9.5 years and median exposure to first treatment with arginine + citrulline, citrulline monotherapy, or arginine monotherapy was 5.5, 2.5, or 0.3 years, respectively. During follow-up, arginine or citrulline was administered at least once (as monotherapy or in combination) in the same proportion of patients (86.1%); the overall median duration of exposure was 5.9 years for arginine + citrulline, 3.1 years for citrulline monotherapy, and 0.6 years for arginine monotherapy. The most common switch was from monotherapy to combination therapy (41 of 75 switches, 54.7%). During treatment, mean ammonia concentrations were 35.9 µmol/L with citrulline, 49.8 µmol/L with arginine, and 53.0 µmol/L with arginine + citrulline. Mean plasma arginine concentrations increased significantly from the beginning to the end of citrulline treatment periods (from 67.6 µmol/L to 84.9 µmol/L, P < 0.05). At last evaluation, mean height and weight for age were normal and most patients showed normal or adapted behavior (98.7%) and normal social life (79.0%). Two patients (2.5%) experienced three treatment-related gastrointestinal adverse reactions. Conclusions This study underlines the importance of citrulline supplementation, either alone or together with arginine, in the management of patients with UCDs. When a monotherapy is considered, citrulline would be the preferred option in terms of increasing plasma arginine concentrations. |
| first_indexed | 2024-03-12T22:13:54Z |
| format | Article |
| id | doaj.art-c41e870d385f45a7bab71242c1c3248d |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-12T22:13:54Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-c41e870d385f45a7bab71242c1c3248d2023-07-23T11:26:32ZengBMCOrphanet Journal of Rare Diseases1750-11722023-07-0118111210.1186/s13023-023-02800-8Citrulline in the management of patients with urea cycle disordersApolline Imbard0Juliette Bouchereau1Jean-Baptiste Arnoux2Anaïs Brassier3Manuel Schiff4Claire-Marine Bérat5Clément Pontoizeau6Jean-François Benoist7Constant Josse8François Montestruc9Pascale de Lonlay10Department of Biochemistry, Assistance Publique-Hôpitaux de ParisReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de ParisReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de ParisReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de ParisReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de ParisDepartment of Biochemistry, Assistance Publique-Hôpitaux de ParisDepartment of Biochemistry, Assistance Publique-Hôpitaux de ParisDepartment of Biochemistry, Assistance Publique-Hôpitaux de PariseXYSTATeXYSTATReference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de ParisAbstract Background Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies. Data collection included patient background, treatment details, changes in biochemical parameters (plasma ammonia and amino acids concentrations), decompensations, and patient outcomes. Results Overall, 79 patients (median age at diagnosis, 0.9 months) received citrulline and/or arginine in combination with a restricted protein diet, most with ornithine transcarbamylase (n = 57, 73%) or carbamoyl phosphate synthetase 1 (n = 15, 19%) deficiencies. Most patients also received ammonium scavengers. Median follow-up was 9.5 years and median exposure to first treatment with arginine + citrulline, citrulline monotherapy, or arginine monotherapy was 5.5, 2.5, or 0.3 years, respectively. During follow-up, arginine or citrulline was administered at least once (as monotherapy or in combination) in the same proportion of patients (86.1%); the overall median duration of exposure was 5.9 years for arginine + citrulline, 3.1 years for citrulline monotherapy, and 0.6 years for arginine monotherapy. The most common switch was from monotherapy to combination therapy (41 of 75 switches, 54.7%). During treatment, mean ammonia concentrations were 35.9 µmol/L with citrulline, 49.8 µmol/L with arginine, and 53.0 µmol/L with arginine + citrulline. Mean plasma arginine concentrations increased significantly from the beginning to the end of citrulline treatment periods (from 67.6 µmol/L to 84.9 µmol/L, P < 0.05). At last evaluation, mean height and weight for age were normal and most patients showed normal or adapted behavior (98.7%) and normal social life (79.0%). Two patients (2.5%) experienced three treatment-related gastrointestinal adverse reactions. Conclusions This study underlines the importance of citrulline supplementation, either alone or together with arginine, in the management of patients with UCDs. When a monotherapy is considered, citrulline would be the preferred option in terms of increasing plasma arginine concentrations.https://doi.org/10.1186/s13023-023-02800-8AmmoniaArginineCitrullineUrea cycle disorders |
| spellingShingle | Apolline Imbard Juliette Bouchereau Jean-Baptiste Arnoux Anaïs Brassier Manuel Schiff Claire-Marine Bérat Clément Pontoizeau Jean-François Benoist Constant Josse François Montestruc Pascale de Lonlay Citrulline in the management of patients with urea cycle disorders Orphanet Journal of Rare Diseases Ammonia Arginine Citrulline Urea cycle disorders |
| title | Citrulline in the management of patients with urea cycle disorders |
| title_full | Citrulline in the management of patients with urea cycle disorders |
| title_fullStr | Citrulline in the management of patients with urea cycle disorders |
| title_full_unstemmed | Citrulline in the management of patients with urea cycle disorders |
| title_short | Citrulline in the management of patients with urea cycle disorders |
| title_sort | citrulline in the management of patients with urea cycle disorders |
| topic | Ammonia Arginine Citrulline Urea cycle disorders |
| url | https://doi.org/10.1186/s13023-023-02800-8 |
| work_keys_str_mv | AT apollineimbard citrullineinthemanagementofpatientswithureacycledisorders AT juliettebouchereau citrullineinthemanagementofpatientswithureacycledisorders AT jeanbaptistearnoux citrullineinthemanagementofpatientswithureacycledisorders AT anaisbrassier citrullineinthemanagementofpatientswithureacycledisorders AT manuelschiff citrullineinthemanagementofpatientswithureacycledisorders AT clairemarineberat citrullineinthemanagementofpatientswithureacycledisorders AT clementpontoizeau citrullineinthemanagementofpatientswithureacycledisorders AT jeanfrancoisbenoist citrullineinthemanagementofpatientswithureacycledisorders AT constantjosse citrullineinthemanagementofpatientswithureacycledisorders AT francoismontestruc citrullineinthemanagementofpatientswithureacycledisorders AT pascaledelonlay citrullineinthemanagementofpatientswithureacycledisorders |