Department of Pediatrics, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 15;878(20):1669-72. doi: 10.1016/j.jchromb.2010.01.046. Epub 2010 Feb 11.
Mitochondrial fatty acids beta-oxidation disorder (FAOD) has become popular with development of tandem mass spectrometry (MS/MS) and enzymatic evaluation techniques. FAOD occasionally causes acute encephalopathy or even sudden death in children. On the other hand, hyperpyrexia may also trigger severe seizures or encephalopathy, which might be caused by the defects of fatty acid beta-oxidation (FAO). We investigated the effect of heat stress on FAO to determine the relationship between serious febrile episodes and defect in beta-oxidation of fatty acid in children. Fibroblasts from healthy control and children with various FAODs, were cultured in the medium loaded with unlabelled palmitic acid for 96 h at 37 degrees C or 41 degrees C. Acylcarnitine (AC) profiles in the medium were determined by MS/MS, and specific ratios of ACs were calculated. Under heat stress (at 41 degrees C), long-chain ACs (C12, C14, or C16) were increased, while medium-chain ACs (C6, C8, or C10) were decreased in cells with carnitine palmitoyl transferase II deficiency, very-long-chain acyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency, whereas AC species from short-chain (C4) to long-chain (C16) were barely affected in medium-chain acyl-CoA dehydrogenase and control. While long-chain ACs (C12-C16) were significantly elevated, short to medium-chain ACs (C4-C10) were reduced in multiple acyl-CoA dehydrogenase deficiency. These data suggest that patients with long-chain FAODs may be more susceptible to heat stress compared to medium-chain FAOD or healthy control and that serious febrile episodes may deteriorate long-chain FAO in patients with long-chain FAODs.
线粒体脂肪酸β-氧化障碍（FAOD）随着串联质谱（MS/MS）和酶学评估技术的发展而受到关注。FAOD 偶尔会导致儿童急性脑病甚至猝死。另一方面，高热也可能引发严重的癫痫发作或脑病，这可能是由于脂肪酸β-氧化（FAO）的缺陷引起的。我们研究了热应激对 FAO 的影响，以确定严重发热发作与儿童脂肪酸β-氧化缺陷之间的关系。将来自健康对照和各种 FAOD 患儿的成纤维细胞在含有未标记棕榈酸的培养基中于 37°C 或 41°C 下培养 96 小时。通过 MS/MS 测定培养基中的酰基肉碱（AC）谱，并计算特定的 AC 比值。在热应激（41°C）下，肉碱棕榈酰转移酶 II 缺乏症、极长链酰基辅酶 A 脱氢酶缺乏症和线粒体三功能蛋白缺乏症细胞中的长链 AC（C12、C14 或 C16）增加，而中链 AC（C6、C8 或 C10）减少，而短链（C4）至长链（C16）的 AC 种类在中链酰基辅酶 A 脱氢酶和对照中几乎不受影响。虽然长链 AC（C12-C16）显著升高，但短链至中链 AC（C4-C10）在多种酰基辅酶 A 脱氢酶缺乏症中减少。这些数据表明，与中链 FAOD 或健康对照相比，长链 FAOD 患者可能对热应激更敏感，严重发热发作可能使长链 FAOD 患者的长链 FAO 恶化。
