Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: The importance of enzyme analysis to ascertain true MCAD deficiency
Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: The importance of enzyme analysis to ascertain true MCAD deficiency
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DOI：
10.1007/s10545-007-0492-3
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发表时间：
2008-02-01
影响因子：
4.2
通讯作者：
Reijngoud, D. -J.
中科院分区：
文献类型：
--
作者：
Derks, T. G. J.;Boer, T. S.;Reijngoud, D. -J.
结果是在2003年10月至2005年9月期间，在荷兰使用串联质谱（MS/MS）确定了全人群新生儿中链酰基辅酶a脱氢酶（MCAD）缺乏症筛查。在荷兰北部对新生儿进行了MCAD缺乏症的前瞻性筛查。新生儿血辛酸肉碱（C-8:0）浓度>= 0.3 μ mol/L，开始临床和实验室随访，其中MCAD酶测定起决定性作用。在2年的时间里，对66 216名新生儿进行了MCAD缺乏症调查，并对28名新生儿进行了随访。根据MCAD酶活性（5.0）鉴定出真阳性（n=14），可区分假阳性和真阳性。用苯丙酰辅酶a作为底物测量MCAD活性，进一步区分MCAD缺乏症新生儿和所谓的轻度MCAD缺乏症新生儿。总之，荷兰北部的新生儿MCAD缺乏筛查导致了预测的受影响新生儿数量。以苯丙酰辅酶a为底物测定白细胞或淋巴细胞中MCAD活性，可作为初步阳性筛选试验结果诊断MCAD缺乏的金标准。
The outcome was determined of population-wide neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (MS/MS) in The Netherlands, between October 2003 and September 2005. Prospective population-wide neonatal screening for MCAD deficiency was performed in the northern part of The Netherlands. In newborns with blood octanoylcarnitine (C-8:0) concentrations >= 0.3 mu mol/L, clinical and laboratory follow-up was initiated, including MCAD enzymatic measurements which played a decisive role. In a 2-year period, 66 216 newborns were investigated for MCAD deficiency and follow-up was initiated in 28 newborns. True-positives (n=14) were identified based upon MCAD enzyme activity 5.0 turned out to differentiate between false-positives and true-positives. Measurement of MCAD activity using phenylpropionyl-CoA as a substrate further discriminated between newborns with MCAD deficiency and so-called mild MCAD deficiency. To summarize, neonatal screening for MCAD deficiency in the northern part of The Netherlands resulted in the predicted number of affected newborns. Measurement of MCAD activity in leukocytes or lymphocytes using phenylpropionyl-CoA as a substrate can be regarded as the gold standard to diagnose MCAD deficiency upon initial positive screening test results.