Estrella Jane, Wilcken Bridget, Carpenter Kevin, Bhattacharya Kaustuv, Tchan Michel, Wiley Veronica
Department of Medical Genetics Westmead Hospital, Sydney, Australia.
J Inherit Metab Dis. 2014 Nov;37(6):881-7. doi: 10.1007/s10545-014-9727-2. Epub 2014 Jun 27.
There have been few reports of cases missed by expanded newborn screening. Tandem mass spectrometry was introduced in New South Wales, Australia in 1998 to screen for selected disorders of amino acid, organic acid and fatty acid metabolism. Of 1,500,000 babies screened by 2012, 1:2700 were diagnosed with a target disorder. Fifteen affected babies were missed by testing, and presented clinically or in family studies. In three cases (cobalamin C defect, very-long-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type 1), this led to modification of analyte cut-off values or protocols during the first 3 years. Two patients with intermittent MSUD, two with β-ketothiolase deficiency, two with citrin deficiency, two siblings with arginosuccinic aciduria, two siblings with homocystinuria, and one with cobalamin C defect had analyte values and ratios below the action limits which could not have been detected without unacceptable false-positive rates. A laboratory interpretation error led to missing one case of cobalamin C defect. Reference ranges, regularly reviewed, were not altered. For citrin deficiency, while relevant metabolites are detectable by tandem mass spectrometry, our cut-off values do not specifically screen for that disorder. Most of the missed cases are doing well and with no acute presentations although eight of 15 are likely to have been somewhat adversely affected by a late diagnosis. Analyte ratio and cut-off value optimisations are important, but for some disorders occasional missed cases may have to be tolerated to maintain an acceptable specificity, and avoid harm from screening.
关于扩大新生儿筛查漏诊病例的报道很少。1998年，串联质谱法在澳大利亚新南威尔士州被引入，用于筛查特定的氨基酸、有机酸和脂肪酸代谢紊乱疾病。到2012年，在接受筛查的150万名婴儿中，每2700名中有1名被诊断出患有目标疾病。有15名受影响的婴儿在检测中被漏诊，他们是在临床就诊或家庭研究中被发现的。在3例病例中（钴胺素C缺陷、极长链酰基辅酶A脱氢酶缺乏症和1型戊二酸尿症），这导致在最初3年内对分析物临界值或检测方案进行了修改。2例间歇性枫糖尿症患者、2例β-酮硫解酶缺乏症患者、2例citrin缺乏症患者、2例患有精氨琥珀酸尿症的兄弟姐妹、2例患有同型胱氨酸尿症的兄弟姐妹以及1例钴胺素C缺陷患者的分析物值和比率低于行动限值，如果不接受不可接受的假阳性率，这些情况是无法检测到的。一次实验室解读错误导致漏诊1例钴胺素C缺陷病例。定期审查的参考范围未作更改。对于citrin缺乏症，虽然相关代谢物可通过串联质谱法检测到，但我们的临界值并未专门针对该疾病进行筛查。大多数漏诊病例情况良好，没有急性发作表现，不过15例中有8例可能因诊断延迟而受到了一定程度的不利影响。分析物比率和临界值的优化很重要，但对于某些疾病，可能不得不容忍偶尔的漏诊病例，以维持可接受的特异性，并避免筛查带来的危害。
