Al-Thihli Khalid, Sinclair Graham, Sirrs Sandra, Mezei Michelle, Nelson Judie, Vallance Hilary
Division of Biochemical Diseases, BC Children's Hospital, 4500 Oak St, Vancouver, BC, Canada.
J Inherit Metab Dis. 2014 Mar;37(2):207-13. doi: 10.1007/s10545-012-9578-7. Epub 2013 Jan 8.
Plasma/serum and dried blood spot (DBS) acylcarnitine profiles (ACPs) are key to the diagnosis of mitochondrial fatty acid β-oxidation disorders (FAODs). Despite their significant clinical applications, limited published data exists to compare their sensitivities and specificities. We retrospectively evaluated these two methods in adult patients with a history of rhabdomyolysis; investigated for an underlying FAOD.
A retrospective study was completed for adult patients (investigated between 2003 and 2011) meeting the inclusion criteria of a history of recurrent rhabdomyolysis or one episode of rhabdomyolysis with a history of exercise intolerance. All subjects underwent investigations for an underlying FAOD including DBS and serum ACP analysis concurrently collected during a symptom-free period, and skin biopsy for cultured fibroblast fatty acid oxidation studies or enzyme activity measurement, as indicated, with or without molecular confirmation. Their medical records were reviewed, and the performance of the two methods were compared.
Seven out of 31 subjects (22.6 %) were diagnosed with an underlying FAOD. Long chain acylcarnitines were more markedly elevated in serum samples from confirmed CPTII cases (n = 4) as compared to matched DBS profiles. The sensitivity and specificity of DBS ACP was 71.4 % (95 % CI, 0.30-0.95) and 100 % (95 % CI, 0.79-1.00), respectively, compared to a sensitivity of 100 % (95 % CI, 0.56-1.00) and a specificity of 94.7 % (95 % CI, 0.72-1.00) for serum ACP.
FAODs appear to be a common cause of recurrent rhabdomyolysis or rhabdomyolysis with a history of exercise induced myalgia. At least historically, FAODs maybe underdiagnosed in adults with rhabdomyolysis. This study suggests that serum ACP might be more sensitive than DBS ACP for detection of an underlying FAOD in adults with rhabdomyolysis while asymptomatic.
血浆/血清和干血斑（DBS）酰基肉碱谱（ACP）是诊断线粒体脂肪酸β氧化障碍（FAODs）的关键。尽管它们有重要的临床应用，但比较其敏感性和特异性的已发表数据有限。我们回顾性评估了这两种方法在有横纹肌溶解病史的成年患者中的应用；对潜在的FAOD进行调查。
对符合复发性横纹肌溶解病史或有运动不耐受病史的一次横纹肌溶解发作纳入标准的成年患者（2003年至2011年期间接受调查）完成一项回顾性研究。所有受试者均接受了潜在FAOD的调查，包括在无症状期同时采集DBS和血清ACP分析，以及根据需要进行皮肤活检以进行培养成纤维细胞脂肪酸氧化研究或酶活性测量，有无分子确认。查阅他们的病历，并比较这两种方法的性能。
31名受试者中有7名（22.6%）被诊断为潜在的FAOD。与匹配的DBS谱相比，确诊的CPTII病例（n = 4）的血清样本中长链酰基肉碱升高更为明显。DBS ACP的敏感性和特异性分别为71.4%（95%CI，0.30 - 0.95）和100%（95%CI，0.79 - 1.00），而血清ACP的敏感性为100%（95%CI，0.56 - 1.00），特异性为94.7%（95%CI，0.72 - 1.00）。
FAODs似乎是复发性横纹肌溶解或有运动诱发肌痛病史的横纹肌溶解的常见原因。至少从历史上看，FAODs在有横纹肌溶解的成年人中可能诊断不足。这项研究表明，对于无症状的有横纹肌溶解的成年人，血清ACP在检测潜在的FAOD方面可能比DBS ACP更敏感。
