Background

Distinguishing systemic metabolic disruptions in maple syrup urine disease (MSUD) beyond amino acid pathways is under-investigated, yet important to understanding disease pathology and treatment options.

Methods

An adolescent female (15 years) with MSUD without liver transplant, attended 2 study visits, 5 days apart. Medical diet adherence was determined based on her 3-day diet records and plasma branched-chain amino acid (BCAA) concentrations at both study visits. Plasma from a single age- and sex-matched control (MURDOCK Study, Duke University) and the case patient were analyzed with UPLC/MS/MS for intensity (m/z), annotated, and normalized against a median of 1 (Metabolon, Morrisville NC). Differences between case/control and 5-day comparisons were defined as ≥ ǀ 0.5 ǀ.

Results

434 lipid metabolites were identified across samples; 90 (20.7%) were higher and 120 (27.6%) lower in the MSUD case at baseline compared with control. By study visit 2, plasma BCAA had declined, while 48 (53%) of elevated lipids and 14 (11.7%) of lower lipid values had moved to within ǀ 0.5 ǀ of control. Most shifts towards control by day 5 were seen in long-chain fatty acid intermediates (42%) and acylcarnitines (32%). Although androgenic (28%) and bile acid (23%) metabolites increased towards control, neither reached control level by day 5.

Discussion

This comparative metabolomics study in a single MSUD case and healthy control suggests intrinsic differences in MSUD lipid metabolism potentially influenced by therapeutic diet. Findings suggest influences on hormone regulation, fatty acid oxidation, and bile acid synthesis, but further studies are needed to confirm an association between MSUD and lipid dysregulation.

Synopsis

Within 5 days of improved dietary adherence, a single MSUD case experienced substantial changes in lipid markers potentially related to changes in plasma branched-chain amino acids.

中文翻译：

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在改善受控支链氨基酸 (BCAA) 饮食依从性 5 天后，枫糖浆尿病 (MSUD) 单例研究的脂质变化

背景

区分氨基酸途径以外的枫糖浆尿病 (MSUD) 中的全身性代谢紊乱尚未得到充分研究，但对于了解疾病病理学和治疗方案很重要。

方法

一名患有 MSUD 且未进行肝移植的青春期女性（15 岁）参加了 2 次研究访问，间隔 5 天。根据她在两次研究访问中的 3 天饮食记录和血浆支链氨基酸 (BCAA) 浓度确定医疗饮食依从性。使用 UPLC/MS/MS 分析来自单一年龄和性别匹配对照（杜克大学 MURDOCK 研究）和病例患者的血浆强度 ( m / z )、注释和标准化中位数 1（Metabolon，北卡罗来纳州莫里斯维尔）。病例/对照和 5 天比较之间的差异定义为 ≥ ǀ 0.5 ǀ。

结果

在样品中鉴定出 434 种脂质代谢物；与对照组相比，基线时 MSUD 病例中有 90 人（20.7%）较高，120 人（27.6%）较低。到第 2 次研究访问时，血浆 BCAA 下降，而 48 (53%) 的血脂升高和 14 (11.7%) 的低血脂值已移动到控制的 ǀ 0.5 ǀ 以内。到第 5 天，大多数向控制的转变发生在长链脂肪酸中间体 (42%) 和酰基肉碱 (32%) 中。尽管雄激素 (28%) 和胆汁酸 (23%) 代谢物向对照增加，但在第 5 天均未达到对照水平。

讨论

这项在单个 MSUD 病例和健康对照中进行的比较代谢组学研究表明，MSUD 脂质代谢的内在差异可能受到治疗性饮食的影响。研究结果表明对激素调节、脂肪酸氧化和胆汁酸合成的影响，但需要进一步的研究来证实 MSUD 与脂质失调之间的关联。

概要

在改善饮食依从性的 5 天内，单个 MSUD 病例的脂质标志物发生了显着变化，这可能与血浆支链氨基酸的变化有关。