Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Room H3160, Stanford, CA 94305, USA.
J Inherit Metab Dis. 2012 Jan;35(1):71-9. doi: 10.1007/s10545-011-9333-5. Epub 2011 May 4.
Maple syrup urine disease (MSUD) was first recognized as an inherited lethal encephalopathy beginning in the first week of life and associated with an unusual odor in the urine of affected children. It was later confirmed as a deficiency of branched-chain keto acid dehydrogenase (BCKDH), which is the second step in branched-chain amino acid (BCAA) breakdown. MSUD is characterized by BCAA and branched-chain keto acid (BCKA) accumulation. BCAAs are essential amino acids and powerful metabolic signals with severe consequences of both deprivation and accumulation. Treatment requires life-long dietary restriction and monitoring of BCAAs. However, despite excellent compliance, children commonly suffer metabolic decompensation during intercurrent illness resulting in life-threatening cerebral edema and dysmyelination. The mechanisms underlying brain injury have been poorly understood. Recent studies using newly developed mouse models of both classic and intermediate MSUD have yielded insight into the consequences of rapid BCAA accumulation. Additionally, these models have been used to test preliminary treatments aimed at competing with blood-brain barrier transport of BCAA using norleucine. Assessment of biochemical changes with and without treatment suggests different roles for BCAA and BCKA in the mechanism of brain injury.
枫糖尿症（MSUD）最初被认为是一种遗传性致死性脑病，始于生命的第一周，并伴有受影响儿童尿液中的异常气味。后来证实其为支链酮酸脱氢酶（BCKDH）缺乏症，这是支链氨基酸（BCAA）分解的第二步。MSUD 的特征是支链氨基酸（BCAA）和支链酮酸（BCKA）的积累。BCAAs 是必需氨基酸和强大的代谢信号，其缺乏和积累都会产生严重后果。治疗需要终生饮食限制和 BCAAs 的监测。然而，尽管有很好的依从性，儿童在并发疾病期间常发生代谢失代偿，导致危及生命的脑水肿和脱髓鞘。导致脑损伤的机制尚未得到很好的理解。最近使用新开发的经典和中间型 MSUD 小鼠模型的研究深入了解了快速 BCAAs 积累的后果。此外，这些模型还用于测试初步治疗，这些治疗旨在使用 norleucine 与血脑屏障转运 BCAAs 竞争。有和没有治疗的生化变化评估表明，BCAA 和 BCKA 在脑损伤机制中发挥不同的作用。
