Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Division of Neuropaediatrics and Metabolic Medicine, Centre for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
J Inherit Metab Dis. 2019 Nov;42(6):1162-1175. doi: 10.1002/jimd.12066. Epub 2019 Feb 27.
Organic acidurias (OAD) and urea-cycle disorders (UCD) are rare inherited disorders affecting amino acid and protein metabolism. As dietary practice varies widely, we assessed their long-term prescribed dietary treatment against published guideline and studied plasma amino acids levels. We analyzed data from the first visit recorded in the European registry and network for intoxication type metabolic diseases (E-IMD, Chafea no. 2010 12 01). In total, 271 methylmalonic aciduria (MMA) and propionic aciduria (PA) and 361 UCD patients were included. Median natural protein prescription was consistent with the recommended daily allowance (RDA), plasma L-valine (57%), and L-isoleucine (55%) levels in MMA and PA lay below reference ranges. Plasma levels were particularly low in patients who received amino acid mixtures (AAMs-OAD) and L-isoleucine:L-leucine:L-valine (BCAA) ratio was 1.0:3.0:3.2. In UCD patients, plasma L-valine, L-isoleucine, and L-leucine levels lay below reference ranges in 18%, 30%, and 31%, respectively. In symptomatic UCD patients who received AAM-UCD, the median natural protein prescription lay below RDA, while their L-valine and L-isoleucine levels and plasma BCAA ratios were comparable to those in patients who did not receive AAM-UCD. Notably, in patients with ornithine transcarbamylase syndrome (OTC-D), carbamylphosphate synthetase 1 syndrome (CPS1-D) and hyperammonemia-hyperornithinemia-homocitrullinemia (HHH) syndrome selective L-citrulline supplementation resulted in higher plasma L-arginine levels than selective L-arginine supplementation. In conclusion, while MMA and PA patients who received AAMs-OAD had very low BCAA levels and disturbed plasma BCAA ratios, AAMs-UCD seemed to help UCD patients obtain normal BCAA levels. In patients with OTC-D, CPS1-D, and HHH syndrome, selective L-citrulline seemed preferable to selective L-arginine supplementation.
有机酸血症（OAD）和尿素循环障碍（UCD）是影响氨基酸和蛋白质代谢的罕见遗传性疾病。由于饮食实践差异很大，我们根据已发表的指南评估了他们长期规定的饮食治疗，并研究了血浆氨基酸水平。我们分析了欧洲中毒型代谢疾病登记处和网络（E-IMD，Chafea no. 2010 12 01）记录的首次就诊数据。共纳入 271 例甲基丙二酸血症（MMA）和丙酸血症（PA）和 361 例 UCD 患者。天然蛋白质的中位数处方符合推荐的日摄入量（RDA），MMA 和 PA 中的血浆 L-缬氨酸（57％）和 L-异亮氨酸（55％）水平低于参考范围。接受氨基酸混合物（AAM-OAD）的患者血浆水平特别低，L-异亮氨酸：L-亮氨酸：L-缬氨酸（BCAA）比值为 1.0:3.0:3.2。在 UCD 患者中，18％、30％和 31％的患者血浆 L-缬氨酸、L-异亮氨酸和 L-亮氨酸水平低于参考范围。接受 AAM-UCD 的有症状 UCD 患者的中位数天然蛋白质处方低于 RDA，而他们的 L-缬氨酸和 L-异亮氨酸水平以及血浆 BCAA 比值与未接受 AAM-UCD 的患者相当。值得注意的是，在瓜氨酸血症（OTC-D）、氨甲酰磷酸合成酶 1 缺乏症（CPS1-D）和高氨血症-高鸟氨酸血症-同型瓜氨酸血症（HHH）综合征患者中，选择性 L-瓜氨酸补充导致的血浆 L-精氨酸水平高于选择性 L-精氨酸补充。总之，接受 AAMs-OAD 的 MMA 和 PA 患者的 BCAA 水平非常低，血浆 BCAA 比值失调，而 AAMs-UCD 似乎有助于 UCD 患者获得正常的 BCAA 水平。在 OTC-D、CPS1-D 和 HHH 综合征患者中，选择性 L-瓜氨酸似乎优于选择性 L-精氨酸补充。
