Newborn screening algorithm distinguishing potential symptomatic isovaleric acidemia from asymptomatic newborns.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Rachel Rock, Oded Rock, Suha Daas, Vered Biton-Regev, Nadav Sagiv, Nasser Abu Salah, Yair Anikster, Ortal Barel, Ronen Hady Cohen, Elena Dumin, Aviva Fattal-Valevski, Tzipora Falik-Zaccai, Eli Herskovitz, Sagi Josefsberg, Hatem Khammash, Katya Kneller, Stanley H Korman, Yuval E Landau, Tally Lerman-Sagie, Hanna Mandel, Elon Pras, Haike Reznik-Wolf, Avraham Shaag, Nava Shaul Lotan, Ronen Spiegel, Galit Tal, Orna Staretz-Chacham, Yael Wilnai, Shlomo Almashanu
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引用次数: 0

Abstract

Newborn screening (NBS) for isovaleric acidemia (IVA) reduces mortality and morbidity; however, it has also resulted in the detection of individuals with an asymptomatic or mild presentation for which early detection via newborn screening has not been proven to alter neurological outcome. We reevaluated biochemical and molecular data for newborns flagged positive for IVA in aim of developing a new screening algorithm to exclude the latter from positive screening. Among 2 794 365 newborns underwent routine newborn screening in Israel, 412 flagged positive for IVA, of which, 371 were false positives on recall sample testing and 41 positive newborns were referred to the clinic. 38/41 have biochemical and molecular confirmation in keeping with IVA. Among the 38 patients, 32% (12/38) were classified as symptomatic while, 68% (26/38) were classified as asymptomatic. 69% of the latter group harbor the known variant associated with mild potentially asymptomatic phenotype, c.932C>T; p. Ala311Val. Among asymptomatic patients, only 46% (12/26) are currently treated. Two novel variants have been detected in the IVD gene: c.487G>A; p. Ala163Thr and c.985A>G; p. Met329Val. Cut-off recalculation, of referred newborns' initial biochemical results, after classifying the referred patients to two binary groups of symptomatic and asymptomatic, resulted in an improved NBS algorithm comprising of C5 >5 μM and C5/C2>0.2 and C5/C3>4 flagging only those likely to have the classic symptomatic phenotype.

区分潜在无症状异戊酸血症和无症状新生儿的新生儿筛查算法。
新生儿异戊酸血症(IVA)筛查(NBS)降低了死亡率和发病率,但也发现了一些无症状或症状轻微的患者,而通过新生儿筛查及早发现这些患者并不能改变神经系统的预后。我们重新评估了被标记为 IVA 阳性的新生儿的生化和分子数据,旨在制定一种新的筛查算法,将后者从阳性筛查中排除。在以色列接受常规新生儿筛查的 2 794 365 名新生儿中,有 412 名标示 IVA 阳性,其中 371 名在召回样本检测中为假阳性,41 名阳性新生儿被转诊至诊所。其中 38/41 例经生化和分子鉴定确认为 IVA。在这 38 名患者中,32%(12/38)被归类为有症状,而 68%(26/38)被归类为无症状。后者中有 69% 的患者携带与轻度潜在无症状表型相关的已知变异,即 c.932C>T; p. Ala311Val。在无症状患者中,只有 46%(12/26)的患者目前正在接受治疗。在 IVD 基因中发现了两个新变异:c.487G>A; p. Ala163Thr 和 c.985A>G; p. Met329Val。在将转诊患者分为有症状和无症状两个二元组后,对转诊新生儿的初始生化结果进行了临界值重新计算,从而改进了 NBS 算法,该算法包括 C5 >5 μM、C5/C2 >0.2 和 C5/C3>4,只标记那些可能具有典型症状表型的患者。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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