Yeo Mildrid, Rehsi Preeya, Yeo Jie Ming, Dixon Marjorie, Chakrapani Anupam
Department of Paediatric Inherited Metabolic Disease, Great Ormond Street Hospital for Children, NHS Foundation Trust and Institute for Child Health, London, UK.
Dietetics, Great Ormond Street Hospital for Children, NHS Foundation Trust and Institute for Child Health, London, UK.
Mol Genet Metab Rep. 2025 Jan 17;42:101190. doi: 10.1016/j.ymgmr.2025.101190. eCollection 2025 Mar.
Branched-chain amino acids (BCAAs) are important for normal growth, development, and function. In urea cycle disorders (UCDs), plasma BCAA levels can be relatively low; this has been attributed variously to low protein intake, hyperammonaemia, and nitrogen scavenger treatment. We undertook a retrospective review of plasma BCAA levels in individuals with UCDs comprising ornithine carbamoyltransferase deficiency (OTCD = 22), arginosuccinate lyase deficiency (ASLD = 12), and argininosuccinate synthase deficiency (ASSD = 6). Scavenger treatment groups comprised sodium benzoate (NaBz, = 20), sodium phenylbutyrate (NaPBA, = 5), NaBz+NaPBA ( = 14), and a control group receiving neither NaBz nor NaPBA (n = 14). In these treatment groups, respectively, median (IQR) plasma levels of leucine were 54 (32), 55 (25), 58 (19), and 91 (70) μmol/L (leucine was lower in the NaBz group than the control, = 0.0282) and numbers of individuals (%) with leucine below normal were 10/20 (50 %), 1/4 (25 %), 10/14 (71 %), and 2/9 (20 %). The pattern was similar for isoleucine and valine. In the NaBz group, plasma BCAA levels were inversely correlated with protein intake ( ≤ 0.01 to ≤ 0.001), plasma ammonia level (p ≤ 0.01 to ≤ 0.0001), and scavenger dose (p ≤ 0.0001). We speculate that individuals with greater disease severity may be prone to BCAA deficiency, caused by BCAA consumption when alternative urea disposal pathways are used. Practical reflections on our audit were that to increase the proportion of plasma BCAA levels in the normal range, we needed to alter the biological value of protein intake, prescribe higher doses of scavenger to facilitate safe levels of protein intake, and give EAA supplements if indicated.
支链氨基酸（BCAAs）对正常生长、发育和功能很重要。在尿素循环障碍（UCDs）中，血浆BCAA水平可能相对较低；这被归因于蛋白质摄入不足、高氨血症和氮清除剂治疗等多种因素。我们对患有UCDs的个体的血浆BCAA水平进行了回顾性研究，这些个体包括鸟氨酸氨甲酰基转移酶缺乏症（OTCD = 22例）、精氨酸琥珀酸裂解酶缺乏症（ASLD = 12例）和精氨酸琥珀酸合成酶缺乏症（ASSD = 6例）。清除剂治疗组包括苯甲酸钠（NaBz，= 20例）、苯丁酸钠（NaPBA，= 5例）、NaBz + NaPBA（= 14例），以及既未接受NaBz也未接受NaPBA的对照组（n = 14例）。在这些治疗组中，亮氨酸的血浆水平中位数（IQR）分别为54（32）、55（25）、58（19）和91（70）μmol/L（NaBz组的亮氨酸水平低于对照组，P = 0.0282），亮氨酸水平低于正常的个体数量（%）分别为10/20（50%）、1/4（25%）、10/14（71%）和2/9（20%）。异亮氨酸和缬氨酸的情况类似。在NaBz组中，血浆BCAA水平与蛋白质摄入量（P≤0.01至P≤0.001）、血浆氨水平（P≤0.01至P≤0.0001）和清除剂剂量（P≤0.0001）呈负相关。我们推测，疾病严重程度较高的个体可能容易出现BCAA缺乏，这是由于在使用替代尿素处理途径时BCAA被消耗所致。我们审计的实际思考是，为了提高血浆BCAA水平在正常范围内的比例，我们需要改变蛋白质摄入的生物价值，开出更高剂量的清除剂以促进安全的蛋白质摄入量，如果有指征则给予必需氨基酸补充剂。
