Schmidt-Sommerfeld E, Penn D, Rinaldo P, Kossak D, Li B U, Huang Z H, Gage D A
Department of Pediatrics, University of Chicago, Pritzker School of Medicine, Illionis 60637.
Pediatr Res. 1992 Jun;31(6):545-51. doi: 10.1203/00006450-199206000-00002.
To determine the sensitivity and specificity of detecting urinary medium-chain acylcarnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic exchange/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexanoylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving valproic acid had a similar acylcarnitine excretion pattern. To further examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were studied. Most of these also tested positive for MCAD deficiency by the above criterion. Analysis by a new gas chromatographic-mass spectrometric procedure revealed that octanoylcarnitine, not valproylcarnitine, was the most abundant medium-chain carnitine ester excreted by a patient treated with valproic acid. Quantitation of urinary hexanoylcarnitine and octanoylcarnitine showed considerable overlap among patients with MCAD deficiency and those receiving valproic acid or a medium-chain triglyceride-enriched diet. MCAD deficiency can be reliably detected in urine specimens by this method without the need for prior carnitine loading. However, other defects in fatty acid oxidation must be differentiated from MCAD deficiency, and a history of medium-chain triglyceride or valproic acid administration must be considered if the diagnosis of MCAD deficiency is sought through analysis of urinary acylcarnitines.
为确定检测尿中中链酰基肉碱对诊断中链酰基辅酶A脱氢酶（MCAD）缺乏症的敏感性和特异性，采用放射性同位素交换/高效液相色谱法，对75例患有代谢性疾病的儿童及对照的114份尿标本进行了盲法分析。所有47例MCAD缺乏症患者均根据己酰肉碱或辛酰肉碱峰面积大于其他中链酰基肉碱峰面积的标准被正确诊断。其中大多数患者是在未服用L-肉碱的无症状状态下接受检测的。4例患有其他脂肪酸氧化缺陷的患者和3例服用丙戊酸的患者有相似的酰基肉碱排泄模式。为进一步检验该方法的特异性，研究了8例食用富含中链甘油三酯饮食的婴儿以及另外13例服用丙戊酸的患者。根据上述标准，这些患者中的大多数检测结果也呈MCAD缺乏症阳性。通过一种新的气相色谱-质谱法分析发现，辛酰肉碱而非丙戊酰肉碱是服用丙戊酸患者排泄的最丰富的中链肉碱酯。尿中己酰肉碱和辛酰肉碱的定量分析显示，MCAD缺乏症患者与服用丙戊酸或富含中链甘油三酯饮食的患者之间存在相当大的重叠。用该方法无需预先服用肉碱即可在尿标本中可靠地检测出MCAD缺乏症。然而，必须将其他脂肪酸氧化缺陷与MCAD缺乏症区分开来，如果通过分析尿酰基肉碱来诊断MCAD缺乏症，则必须考虑中链甘油三酯或丙戊酸的用药史。
