Nutrition Department, Clinical Center.
Organic Acid Research Section, Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Clin Nutr Metab Care. 2018 Jan;21(1):42-48. doi: 10.1097/MCO.0000000000000428.
The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices.
Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods. The combination of protein restriction and medical food use in MMA and propionic acidemia results in an imbalanced branched-chain amino acid (BCAA) dietary content with a high Leu-to-Val and/or Ile ratio. This leads to decreased plasma levels of Val and Ile and predicts impaired brain uptake of multiple essential amino acids. Decreased transport of methionine (Met) across the blood-brain barrier due to high circulating Leu levels is of particular concern in cblC deficiency in which endogenous Met synthesis is impaired.
Investigations into the optimal composition of medical foods for MMA and propionic acidemia, and potential scenarios in which Leu supplementation may be beneficial are needed. Until then, MMA/propionic acidemia medical foods should be used judiciously in the dietary management of these patients and avoided altogether in cblC deficiency.
本综述重点介绍富含亮氨酸（Leu）且不含缬氨酸（Val）和异亮氨酸（Ile）的医学食品在治疗甲基丙二酸血症（MMA）、丙酸血症和钴胺素 C（cblC）缺乏症中的多种作用，旨在推进饮食实践。
亮氨酸是一种关键的代谢调节剂，对不同的器官系统有多种影响。最近的观察性研究表明，由于医学食品的广泛使用，这些影响可能会对 MMA 患者产生意想不到的后果。MMA 和丙酸血症中蛋白质限制和医学食品的使用相结合，导致支链氨基酸（BCAA）饮食含量不平衡，亮氨酸与缬氨酸和/或异亮氨酸的比值较高。这导致 Val 和 Ile 的血浆水平降低，并预测多种必需氨基酸的脑摄取受损。由于循环亮氨酸水平升高，甲硫氨酸（Met）穿过血脑屏障的转运减少，这在 cblC 缺乏症中尤为重要，因为内源性 Met 合成受损。
需要研究 MMA 和丙酸血症医学食品的最佳成分，以及亮氨酸补充可能有益的潜在情况。在这之前，MMA/丙酸血症医学食品应谨慎用于这些患者的饮食管理，并且在 cblC 缺乏症中应完全避免。
