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首页> 外文期刊>International Journal of Neonatal Screening >Fibroblast Fatty-Acid Oxidation Flux Assays Stratify Risk in Newborns with Presumptive-Positive Results on Screening for Very-Long Chain Acyl-CoA Dehydrogenase Deficiency
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Fibroblast Fatty-Acid Oxidation Flux Assays Stratify Risk in Newborns with Presumptive-Positive Results on Screening for Very-Long Chain Acyl-CoA Dehydrogenase Deficiency

机译：成纤维细胞脂肪酸氧化通量测定法在筛查超长链酰基辅酶A脱氢酶缺乏症的推定阳性结果中分层了新生儿的风险

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Very-long chain acyl-CoA dehydrogenase deficiency (VLCADD) is a clinically heterogeneous disorder with three major phenotypes: severe neonatal/infantile, milder childhood and late onset myopathic. VLCADD is genetically heterogeneous with numerous pathogenic mutations and variants of uncertain significance. VLCADD is included in many newborn screening programs but these suffer from high false positive rates, primarily due to positive screens in heterozygotes. Separating these and newborns with two low-risk ?￠????mild?￠???? variants from clinically at risk patients can be problematic, as clinical and biochemical markers are often unreliable, particularly in stable neonates. We have measured fibroblast fatty acid oxidation flux using [9,10-H 3 ]myristic acid and [9,10-H 3 ]oleic acid from 69 clinically presenting VLCADD patients including myopathic and infantile phenotypes and 13 positive newborn screened patients. We also measured fibroblast VLCADD enzyme activity by UV-HPLC detection of product in a sub-set of patients and compared these results to oleate FAO-flux. Fibroblast enzyme assay by UV-HPLC detection failed to clearly discriminate between some clinically presenting VLCADD patient cell lines and cell lines from some simple heterozygotes. FAO-flux clearly discriminated between clinically presenting VLCADD patients and the false positive screened patients. FAO-flux at 37 ???°C provides information as to the likely clinical phenotype but FAO-flux at 41 ???°C is the best discriminator for identifying clinically at risk patients.
机译：超长链酰基辅酶A脱氢酶缺乏症（VLCADD）是一种临床异质性疾病，具有三种主要表型：严重的新生儿/婴儿，较轻的儿童期和迟发性肌病。 VLCADD是遗传异质的，具有许多致病性突变和意义不确定的变体。 VLCADD被包括在许多新生儿筛查程序中，但是这些程序具有较高的假阳性率，这主要是由于杂合子中的阳性筛查。将这些婴儿与新生儿隔离开来的是两个低风险的轻度婴儿。临床上有风险的患者的变体可能会出现问题，因为临床和生化标记通常不可靠，尤其是在稳定的新生儿中。我们使用[9,10-H 3]肉豆蔻酸和[9,10-H 3]油酸测定了来自69例临床上表现为VLCADD患者（包括肌病和婴儿表型）和13例阳性新生儿筛查患者的成纤维细胞脂肪酸氧化通量。我们还通过UV-HPLC检测亚组患者的产品来测量成纤维细胞VLCADD酶的活性，并将这些结果与油酸FAO-flux进行了比较。通过UV-HPLC检测进行的成纤维细胞酶测定未能清楚地区分某些临床上出现的VLCADD患者细胞系和某些简单杂合体的细胞系。 FAO-flux清楚地区分了临床表现的VLCADD患者和假阳性筛查患者。在37°C时，FAO-flux提供了有关可能的临床表型的信息，但在41°C时，FAO-flux是识别临床上有风险的患者的最佳区分方法。

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