Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: diagnosis by acylcarnitine analysis in blood.
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DOI：
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发表时间：
1993-05
影响因子：
9.8
通讯作者：
J. L. Hove;Wen Zhang;S. Kahler;C. Roe;Yuan-Tsong Chen;N. Terada;D. Chace;A. K. lafolla;
中科院分区：
文献类型：
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作者：
J. L. Hove;Wen Zhang;S. Kahler;C. Roe;Yuan-Tsong Chen;N. Terada;D. Chace;A. K. lafolla;
中链酰基辅酶A脱氢酶（MCAD）缺乏症是一种常染色体隐性遗传的脂肪酸代谢紊乱。该疾病的特征是与潜在致命性低血糖相关的发作性疾病，并且具有相对较高的频率。一种快速、可靠的诊断MCAD缺陷的方法是非常需要的。通过同位素稀释串联质谱法对62例MCAD缺乏症患者的血浆或全血样本进行特异性酰基肉毒碱分析。还分析了42例MCAD缺乏症患者的未受影响的亲属和其他组血浆C8酰基肉碱升高的患者的酰基肉碱，其中32例接受丙戊酸，9例接受中链甘油三酯补充剂，4例患有多种酰基辅酶A脱氢酶缺乏症，8例其他各种病因。通过酰基肉毒碱分析明确诊断MCAD缺乏的标准是升高的C8-酰基肉毒碱浓度（> 0.3 μ M），C8/C10酰基肉毒碱的比率> 5，并且缺乏链长> C10的升高的种类。这些标准不受临床状态，肉毒碱治疗，或潜在的基因突变，并没有假阳性或假阴性结果。同样的标准也成功应用于从八名患者的原始古特里卡中检索到的新生儿血斑的图谱。因此，通过分析血液中的酰基肉毒碱，包括症状前新生儿识别，可以可靠地诊断MCAD缺乏症。串联质谱法是一种快速、准确测定所有相关酰基肉毒碱种类的简便方法。
Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is a disorder of fatty acid catabolism, with autosomal recessive inheritance. The disease is characterized by episodic illness associated with potentially fatal hypoglycemia and has a relatively high frequency. A rapid and reliable method for the diagnosis of MCAD deficiency is highly desirable. Analysis of specific acylcarnitines was performed by isotope-dilution tandem mass spectrometry on plasma or whole blood samples from 62 patients with MCAD deficiency. Acylcarnitines were also analyzed in 42 unaffected relatives of patients with MCAD deficiency and in other groups of patients having elevated plasma C8 acylcarnitine, consisting of 32 receiving valproic acid, 9 receiving medium-chain triglyceride supplement, 4 having multiple acyl-coenzyme A dehydrogenase deficiency, and 8 others with various etiologies. Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevated C8-acylcarnitine concentration (> 0.3 microM), a ratio of C8/C10 acylcarnitines of > 5, and lack of elevated species of chain length > C10. These criteria were not influenced by clinical state, carnitine treatment, or underlying genetic mutation, and no false-positive or false-negative results were obtained. The same criteria were also successfully applied to profiles from neonatal blood spots retrieved from the original Guthrie cards of eight patients. Diagnosis of MCAD deficiency can therefore be made reliably through the analysis of acylcarnitines in blood, including presymptomatic neonatal recognition. Tandem mass spectrometry is a convenient method for fast and accurate determination of all relevant acylcarnitine species.