Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Humans Ornithine Carbamoyltransferase Deficiency Disease / surgery Hyperammonemia / drug therapy Liver Transplantation Citrulline Carbamyl Phosphate / metabolism Ammonia / metabolism Retrospective Studies Carbamoyl-Phosphate Synthase (Ammonia) / metabolism Arginine / therapeutic use Ornithine Carbamoyltransferase

carbamoyl phosphate synthetase 1 citrulline liver transplantation ornithine transcarbamylase substitution urea cycle disorders

Journal

Journal of inherited metabolic disease

ISSN: 1573-2665

Titre abrégé: J Inherit Metab Dis

Pays: United States

ID NLM: 7910918

Informations de publication

Date de publication:
Mar 2024

Historique:

revised: 12 01 2024

received: 06 08 2023

accepted: 18 01 2024

medline: 18 3 2024

pubmed: 20 2 2024

entrez: 20 2 2024

Statut: ppublish

Résumé

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

Identifiants

DOI: 10.1002/jimd.12717 PMID: 38375550

pubmed: 38375550

doi: 10.1002/jimd.12717

doi:

Substances chimiques

Citrulline 29VT07BGDA

Carbamyl Phosphate 590-55-6

Ammonia 7664-41-7

Carbamoyl-Phosphate Synthase (Ammonia) EC 6.3.4.16

Arginine 94ZLA3W45F

Ornithine Carbamoyltransferase EC 2.1.3.3

Types de publication

Observational Study Multicenter Study Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

220-229

Subventions

Organisme : Ministerstvo Zdravotnictví Ceské Republiky

ID : RVO VFN 64165

Informations de copyright

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