Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency
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Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency. / Aldrian, Denise; Waldner, Birgit; Vogel, Georg F.; El-Gharbawy, Areeg H.; McKiernan, Patrick; Vockley, Jerard; Landau, Yuval E.; Al Mutairi, Fuad; Stepien, Karolina M.; Kwok, Anne Mei Kwun; Yıldız, Yılmaz; Honzik, Tomas; Kelifova, Silvie; Ellaway, Carolyn; Lund, Allan M.; Mori, Mari; Grünert, Sarah C.; Scholl-Bürgi, Sabine; Zöggeler, Thomas; Oberhuber, Rupert; Schneeberger, Stefan; Müller, Thomas; Karall, Daniela.
I: Journal of Inherited Metabolic Disease, Bind 47, Nr. 2, 2024, s. 220-229.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency
AU - Aldrian, Denise
AU - Waldner, Birgit
AU - Vogel, Georg F.
AU - El-Gharbawy, Areeg H.
AU - McKiernan, Patrick
AU - Vockley, Jerard
AU - Landau, Yuval E.
AU - Al Mutairi, Fuad
AU - Stepien, Karolina M.
AU - Kwok, Anne Mei Kwun
AU - Yıldız, Yılmaz
AU - Honzik, Tomas
AU - Kelifova, Silvie
AU - Ellaway, Carolyn
AU - Lund, Allan M.
AU - Mori, Mari
AU - Grünert, Sarah C.
AU - Scholl-Bürgi, Sabine
AU - Zöggeler, Thomas
AU - Oberhuber, Rupert
AU - Schneeberger, Stefan
AU - Müller, Thomas
AU - Karall, Daniela
N1 - Publisher Copyright: © 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - carbamoyl phosphate synthetase 1
KW - citrulline
KW - liver transplantation
KW - ornithine transcarbamylase
KW - substitution
KW - urea cycle disorders
U2 - 10.1002/jimd.12717
DO - 10.1002/jimd.12717
M3 - Journal article
C2 - 38375550
AN - SCOPUS:85186182456
VL - 47
SP - 220
EP - 229
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 2
ER -
ID: 386600718