Citrulline in the management of patients with urea cycle disorders

Orphanet Journal of Rare Diseases

Research

Jean-François Benoist¹  Apolline Imbard¹  Clément Pontoizeau²  Claire-Marine Bérat²  Juliette Bouchereau³  Anaïs Brassier³  Jean-Baptiste Arnoux³  Pascale de Lonlay⁴  Manuel Schiff⁵  François Montestruc⁶  Constant Josse⁶ 

[1] Department of Biochemistry, Assistance Publique-Hôpitaux de Paris, Paris, France;Université Paris-Saclay, Paris, France;Department of Biochemistry, Assistance Publique-Hôpitaux de Paris, Paris, France;Université de Paris, Paris, France;Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, G2M network, MetabERN, Paris, France;Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, G2M network, MetabERN, Paris, France;Université de Paris, Paris, France;Inserm UMR S1151, Institut Necker-Enfants Malades (INEM), Paris, France;Reference Center for Inborn Error of Metabolism, Department of Pediatrics, Necker Hospital, Assistance Publique-Hôpitaux de Paris, G2M network, MetabERN, Paris, France;Université de Paris, Paris, France;Inserm UMR _S1163, Institut Imagine, Paris, France;eXYSTAT, 92240, Malakoff, France;

关键词: Ammonia;    Arginine;    Citrulline;    Urea cycle disorders;   

DOI  :  10.1186/s13023-023-02800-8

 received in 2022-12-07, accepted in 2023-07-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTreatment 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.ResultsOverall, 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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