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.

Adult Inherited Metabolic Diseases Salford Royal Organisation Northern Care Alliance NHS Foundation Trust Salford Greater Manchester UK

Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

Department of General Paediatrics Adolescent Medicine and Neonatology Medical Centre University of Freiburg Faculty of Medicine Freiburg Germany

Department of Paediatrics 1 Medical University of Innsbruck Innsbruck Austria

Department of Pediatrics and Adolescent Medicine Hong Kong Children's Hospital Kowloon Hong Kong

Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University General University Hospital Prague Prague Czech Republic

Department of Pediatrics The Ohio State University College of Medicine Columbus Ohio USA

Department of Pediatrics University of Pittsburgh School of Medicine UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA

Department of Visceral Transplant and Thoracic Surgery Center of Operative Medicine Medical University of Innsbruck Innsbruck Austria

Departments of Clinical Genetics and Pediatrics Center for Inherited Metabolic Diseases Rigshospitalet Copenhagen Denmark

Disciplines of Child and Adolescent Health and Genomic Medicine University of Sydney Sydney Australia

Division of Genetic and Genomic Medicine Nationwide Children's Hospital Columbus Ohio USA

Division of Medical Genetics University of Pittsburgh School of Medicine Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA

Division of Pediatric Metabolism Department of Pediatrics Faculty of Medicine Hacettepe University Ankara Turkey

Genetic Metabolic Disorders Service Sydney Children's Hospital Network Sydney New South Wales Australia

Genetics and Precision Medicine Department King Abdullah Specialized Children Hospital King Abdulaziz Medical City MNG HA Riyadh Saudi Arabia

Institute of Cell Biology Biocenter Medical University of Innsbruck Innsbruck Austria

King Abdullah International Medical Research Center King Saud Bin Abdulaziz University for Health Sciences Ministry of National Guard Health Affairs Riyadh Saudi Arabia

Metabolic Disease Unit Schneider Children's Medical Center of Israel Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

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