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

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Denise Aldrian, Birgit Waldner, Georg F. Vogel, Areeg H. El-Gharbawy, Patrick McKiernan, Jerard Vockley, Yuval E. Landau, Fuad Al Mutairi, Karolina M. Stepien, Anne Mei-Kwun Kwok, Yılmaz Yıldız, Tomas Honzik, Silvie Kelifova, Carolyn Ellaway, Allan M. Lund, Mari Mori, Sarah C. Grünert, Sabine Scholl-Bürgi, Thomas Zöggeler, Rupert Oberhuber, Stefan Schneeberger, Thomas Müller, Daniela Karall
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Abstract

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.

Abstract Image

瓜氨酸替代物对碳酰磷酸合成酶 1 和鸟氨酸转氨酶缺乏症患者肝移植后临床结果的影响。
氨基甲酰基磷酸合成酶 1(CPS1)和鸟氨酸转氨酶(OTC)缺乏症是一种罕见的尿素循环疾病,可导致危及生命的高氨血症。肝移植(LT)是一种可治愈的方法,它提供了一种替代药物治疗和终身饮食限制的方法,而药物治疗和终身饮食限制会带来高氨血症的风险。然而,大多数患者在肝移植后仍会出现代谢异常,尤其是血浆瓜氨酸水平较低,对临床影响值得怀疑。迄今为止,人们对这些变化知之甚少,而且对LT术后是否替代l-瓜氨酸能改善患者症状和预后也未达成共识。在这项多中心、回顾性、观察性研究中,24 名患者因 CPS1(11 人)或 OTC(13 人)缺乏症接受了 LT 治疗,其中 25% 的患者未接受 l-瓜氨酸或精氨酸替代治疗。相关性分析显示,替代剂量与瓜氨酸水平之间没有相关性(CPS1,p = 0.8;OTC,p = 1)。肝移植后的精氨酸水平在LT后正常,与瓜氨酸替代无关。原肝存活对智力损害没有影响(p = 0.67)。回归分析表明,l-瓜氨酸替代与发育不良(p = 0.611)或神经系统结果(p = 0.701)之间没有相关性。氨峰值对智力损害有显著影响(p = 0.017)。CPS1和OTC缺乏症患者LT后的血浆氨峰值水平与智力损害相关。LT后的生长和智力损害与l-瓜氨酸替代无明显关系。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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