Background

The plasma acylcarnitine profile is frequently used as a biochemical assessment for follow-up in diagnosed patients with fatty acid oxidation disorders (FAODs). Disease specific acylcarnitine species are elevated during metabolic decompensation but there is clinical and biochemical heterogeneity among patients and limited data on the utility of an acylcarnitine profile for routine clinical monitoring.

Methods

We evaluated plasma acylcarnitine profiles from 30 diagnosed patients with long-chain FAODs (carnitine palmitoyltransferase-2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxy acyl-CoA dehydrogenase or mitochondrial trifunctional protein (LCHAD/TFP) deficiencies) collected after an overnight fast, after feeding a controlled low-fat diet, and before and after moderate exercise. Our purpose was to describe the variability in this biomarker and how various physiologic states effect the acylcarnitine concentrations in circulation.

Results

Disease specific acylcarnitine species were higher after an overnight fast and decreased by approximately 60% two hours after a controlled breakfast meal. Moderate-intensity exercise increased the acylcarnitine species but it varied by diagnosis. When analyzed for a genotype/phenotype correlation, the presence of the common LCHADD mutation (c.1528G > C) was associated with higher levels of 3-hydroxyacylcarnitines than in patients with other mutations.

Conclusions

We found that feeding consistently suppressed and that moderate intensity exercise increased disease specific acylcarnitine species, but the response to exercise was highly variable across subjects and diagnoses. The clinical utility of routine plasma acylcarnitine analysis for outpatient treatment monitoring remains questionable; however, if acylcarnitine profiles are measured in the clinical setting, standardized procedures are required for sample collection to be of value.

中文翻译：

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禁食、进食和运动对 CPT2D、VLCADD 和 LCHADD/TFPD 受试者血浆酰基肉碱的影响。

背景

血浆酰基肉碱概况经常用作对诊断为脂肪酸氧化障碍 (FAOD) 的患者进行随访的生化评估。疾病特异性酰基肉碱种类在代谢失代偿期间升高，但患者之间存在临床和生化异质性，并且关于酰基肉碱概况用于常规临床监测的效用的数据有限。

方法

我们评估了 30 名确诊患有长链 FAOD（肉碱棕榈酰转移酶 2 (CPT2)、极长链酰基辅酶 A 脱氢酶 (VLCAD) 和长链 3-羟基酰基辅酶 A 脱氢酶或线粒体三功能蛋白）的患者的血浆酰基肉碱概况(LCHAD/TFP) 缺陷）在禁食过夜后、控制低脂饮食后以及适度运动前后收集。我们的目的是描述这种生物标志物的可变性以及各种生理状态如何影响循环中的酰基肉碱浓度。

结果

疾病特异性酰基肉碱种类在禁食过夜后较高，在控制早餐后两小时减少约 60%。中等强度的运动增加了酰基肉碱的种类，但它因诊断而异。当分析基因型/表型相关性时，常见 LCHADD 突变 (c.1528G > C) 的存在与 3-羟基酰基肉碱水平高于其他突变患者相关。

结论

我们发现进食持续抑制，中等强度运动增加疾病特异性酰基肉碱种类，但对运动的反应在不同受试者和诊断之间差异很大。常规血浆酰基肉碱分析在门诊治疗监测中的临床应用仍然值得怀疑；然而，如果在临床环境中测量酰基肉碱概况，则需要标准化程序才能使样本收集有价值。