Language

English

Publication Date

3-18-2026

Journal

Scientific Reports

DOI

10.1038/s41598-026-42150-6

PMID

41851188

PMCID

PMC13291364

PubMedCentral® Posted Date

3-18-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Principles of long-term medical management in individuals with urea cycle disorders (UCDs) encompass (1) a low protein diet, (2) supplementation of arginine and/or citrulline along with essential amino acids, nutrients, vitamins and trace elements, and (3) use of nitrogen scavenging agents to reduce recurrent hyperammonemic events (HAEs). These principles aim at providing metabolic stability, elimimation of chronic complications, and achievement of normal development as well as growth. A retrospective comparative analysis was performed by studying 138 individuals with male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) based on in vitro residual enzymatic activity for severity-adjustment. Results show that individuals with mOTC-D, CTLN1 and ASA are at risk of progressive linear growth impairment, recurrent annual HAEs and an unfavorable neurocognitive outcome despite being under long-term nitrogen scavenging pharmacotherapy. No overall superiority among existing nitrogen scavenging agents with regard to the individual's metabolic stability, linear growth impairment and poor neurocognitive outcome was observed. Novel therapeutic strategies are urgently needed to ultimately improve health outcomes in individuals with UCDs in order to sufficiently meet guideline-specific goals.

Keywords

Humans, Urea Cycle Disorders, Inborn, Nitrogen, Male, Retrospective Studies, Treatment Outcome, Citrullinemia, Ornithine Carbamoyltransferase Deficiency Disease, Argininosuccinic Aciduria, Citrulline, Arginine, Sodium benzoate, Sodium/glycerol phenylbutyrate, Urea cycle disorders, UCDC, E-IMD, Diseases, Medical research, Neurology, Neuroscience

Published Open-Access

yes

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