Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon, United States of America.
Biochemical Genetics Laboratory, Mayo Clinic, Rochester, MN, United States of America.
Mol Genet Metab. 2020 Sep-Oct;131(1-2):90-97. doi: 10.1016/j.ymgme.2020.09.001. Epub 2020 Sep 6.
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.
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.
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.
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.
血浆酰基肉碱谱常用于诊断为脂肪酸氧化障碍（FAOD）的患者的随访中的生化评估。在代谢失代偿期间，特定于疾病的酰基肉碱种类会升高，但患者之间存在临床和生化异质性，并且关于酰基肉碱谱用于常规临床监测的实用性的数据有限。
我们评估了 30 名长链 FAOD 患者（肉碱棕榈酰基转移酶-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（LCHAD/TFP）缺乏症）的血浆酰基肉碱谱，这些患者在禁食过夜后、在控制低脂饮食后、以及在适度运动前后采集。我们的目的是描述该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。
禁食后，特定于疾病的酰基肉碱种类较高，在控制早餐两小时后降低约 60%。适度强度的运动增加了酰基肉碱种类，但因诊断而异。当分析基因型/表型相关性时，常见的 LCHADD 突变（c.1528G>C）的存在与较高水平的 3-羟基酰基肉碱有关，而不是与其他突变的患者。
我们发现进食会持续抑制，而适度强度的运动增加了特定于疾病的酰基肉碱种类，但运动的反应在受试者和诊断之间高度可变。常规血浆酰基肉碱分析用于门诊治疗监测的临床实用性仍存在疑问；然而，如果在临床环境中测量酰基肉碱谱，则需要标准化的样本采集程序才能有价值。
