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J Inherit Metab Dis ; 47(2): 220-229, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38375550

RESUMO

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.


Assuntos
Hiperamonemia , Transplante de Fígado , Doença da Deficiência de Ornitina Carbomoiltransferase , Humanos , Doença da Deficiência de Ornitina Carbomoiltransferase/cirurgia , Hiperamonemia/tratamento farmacológico , Citrulina , Carbamoil-Fosfato/metabolismo , Carbamoil-Fosfato/uso terapêutico , Amônia/metabolismo , Estudos Retrospectivos , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Arginina/uso terapêutico , Ornitina Carbamoiltransferase
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