Spiekerkoetter Ute, Sun Bin, Zytkovicz Thomas, Wanders Ronald, Strauss Arnold W, Wendel Udo
Vanderbilt University School of Medicine, Department of Pediatrics, Nashville, Tennessee, 37232, USA.
J Pediatr. 2003 Sep;143(3):335-42. doi: 10.1067/S0022-3476(03)00292-0.
To determine whether asymptomatic persons with biochemical evidence of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency identified through expanded newborn screening with tandem mass spectometry have confirmed disease.
We characterized 8 asymptomatic VLCAD-deficient individuals by enzyme and/or mutational analysis and compared them with clinically diagnosed, symptomatic patients with regard to mutations, enzyme activity, phenotype, and age of disease onset.
VLCAD molecular analyses in 6 unrelated patients revealed the previously reported V243A mutation, associated with hepatic or myopathic phenotypes, on 7/12 alleles. All other mutations were also missense mutations. Residual VLCAD activities of 6% to 11% of normal were consistent with milder phenotypes. In these identified individuals treated prospectively with dietary modification as preventive measures, clinical symptoms did not develop during follow-up.
MS/MS-based newborn screening correctly identifies VLCAD-deficient individuals. Based on mutational and enzymatic findings, these infants probably are at risk of future disease. Because life-threatening metabolic derangement can occur even in otherwise mild phenotypes, we advocate universal newborn screening programs for VLCAD deficiency to detect affected patients and prevent development of metabolic crises. Longer-term follow-up is essential to define outcomes, the definite risk of future disease, and appropriate treatment recommendations.
确定通过串联质谱法进行扩大新生儿筛查而发现的具有极长链酰基辅酶A脱氢酶（VLCAD）缺乏生化证据的无症状个体是否确诊患病。
我们通过酶和/或突变分析对8名无症状的VLCAD缺乏个体进行了特征描述，并将他们在突变、酶活性、表型和发病年龄方面与临床诊断的有症状患者进行了比较。
对6名无亲缘关系患者的VLCAD分子分析显示，在7/12个等位基因上发现了先前报道的与肝型或肌病型表型相关的V243A突变。所有其他突变也均为错义突变。残余VLCAD活性为正常的6%至11%，与较轻的表型一致。在这些经前瞻性饮食调整作为预防措施治疗的已确诊个体中，随访期间未出现临床症状。
基于串联质谱的新生儿筛查能够正确识别VLCAD缺乏个体。根据突变和酶学研究结果，这些婴儿未来可能有患病风险。由于即使在其他方面为轻度表型的情况下也可能发生危及生命的代谢紊乱，我们主张针对VLCAD缺乏开展普遍的新生儿筛查项目，以检测受影响的患者并预防代谢危机的发生。长期随访对于明确预后、未来疾病的确切风险以及合适的治疗建议至关重要。
