Single centre retrospective review of plasma branched-chain amino acid levels in children with urea cycle disorders: Impact of treatment modalities and disease severity

Abstract

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 n = 22), arginosuccinate lyase deficiency (ASLD n = 12), and argininosuccinate synthase deficiency (ASSD n = 6). Scavenger treatment groups comprised sodium benzoate (NaBz, n = 20), sodium phenylbutyrate (NaPBA, n = 5), NaBz+NaPBA (n = 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, p = 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 (p ≤ 0.01 to p ≤ 0.001), plasma ammonia level (p ≤ 0.01 to p ≤ 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.