Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Inherited Metabolic Disease Pub Date : 2024-04-02 DOI:10.1002/jimd.12731

Anna T. Reischl-Hajiabadi, Elena Schnabel, Florian Gleich, Katharina Mengler, Martin Lindner, Peter Burgard, Roland Posset, Svenja Lommer-Steinhoff, Sarah C. Grünert, Eva Thimm, Peter Freisinger, Julia B. Hennermann, Johannes Krämer, Gwendolyn Gramer, Dominic Lenz, Stine Christ, Friederike Hörster, Georg F. Hoffmann, Sven F. Garbade, Stefan Kölker, Ulrike Mütze

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引用次数: 0

Abstract

The current German newborn screening (NBS) panel includes 13 inherited metabolic diseases (IMDs). In addition, a NBS pilot study in Southwest Germany identifies individuals with propionic acidemia (PA), methylmalonic acidemia (MMA), combined and isolated remethylation disorders (e.g., cobalamin [cbl] C and methylenetetrahydrofolate reductase [MTHFR] deficiency), cystathionine β-synthase (CBS) deficiency, and neonatal cbl deficiency through one multiple-tier algorithm. The long-term health benefits of screened individuals are evaluated in a multicenter observational study. Twenty seven screened individuals with IMDs (PA [N = 13], MMA [N = 6], cblC deficiency [N = 5], MTHFR deficiency [N = 2] and CBS deficiency [N = 1]), and 42 with neonatal cbl deficiency were followed for a median of 3.6 years. Seventeen screened IMD patients (63%) experienced at least one metabolic decompensation, 14 of them neonatally and six even before the NBS report (PA, cbl-nonresponsive MMA). Three PA patients died despite NBS and immediate treatment. Fifteen individuals (79%) with PA or MMA and all with cblC deficiency developed permanent, mostly neurological symptoms, while individuals with MTHFR, CBS, and neonatal cbl deficiency had a favorable clinical outcome. Utilizing a combined multiple-tier algorithm, we demonstrate that NBS and specialized metabolic care result in substantial benefits for individuals with MTHFR deficiency, CBS deficiency, neonatal cbl deficiency, and to some extent, cbl-responsive MMA and cblC deficiency. However, its advantage is less evident for individuals with PA and cbl-nonresponsive MMA.

Synopsis

Early detection through newborn screening and subsequent specialized metabolic care improve clinical outcomes and survival in individuals with MTHFR deficiency and cystathionine-β-synthase deficiency, and to some extent in cobalamin-responsive methylmalonic acidemia (MMA) and cblC deficiency while the benefit for individuals with propionic acidemia and cobalamin-nonresponsive MMA is less evident due to the high (neonatal) decompensation rate, mortality, and long-term complications.

Abstract Image

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新生儿丙酸血症、甲基丙二酸血症和同型半胱氨酸尿症筛查结果。

德国目前的新生儿筛查（NBS）项目包括 13 种遗传代谢病（IMDs）。此外，德国西南部的一项 NBS 试点研究通过一种多层次算法识别丙酸血症 (PA)、甲基丙二酸血症 (MMA)、合并和分离性再甲基化障碍（如钴胺素 [cbl] C 和亚甲基四氢叶酸还原酶 [MTHFR] 缺乏症）、胱硫醚 β 合成酶 (CBS) 缺乏症和新生儿 cbl 缺乏症患者。在一项多中心观察研究中，对接受筛查者的长期健康益处进行了评估。研究人员对 27 名接受筛查的 IMD 患者（PA [N = 13]、MMA [N = 6]、cblC 缺乏症 [N = 5]、MTHFR 缺乏症 [N = 2] 和 CBS 缺乏症 [N = 1]）和 42 名新生儿 cbl 缺乏症患者进行了中位 3.6 年的随访。17 名筛查出的 IMD 患者（63%）至少出现过一次代谢失调，其中 14 人在新生儿期出现，6 人甚至在 NBS 报告之前就出现了代谢失调（PA，cbl 无反应 MMA）。尽管进行了 NBS 并立即进行了治疗，但仍有三名 PA 患者死亡。15名 PA 或 MMA 患者（79%）和所有 cblC 缺乏症患者都出现了永久性症状，主要是神经系统症状，而 MTHFR、CBS 和新生儿 cbl 缺乏症患者的临床结局良好。利用多层次联合算法，我们证明了 NBS 和专门的代谢护理可为 MTHFR 缺乏症、CBS 缺乏症、新生儿 cbl 缺乏症患者带来巨大益处，在一定程度上也可为 cbl 反应性 MMA 和 cblC 缺乏症患者带来益处。然而，对于 PA 和 cbl 无反应的 MMA 患者，其优势就不那么明显了。简述：通过新生儿筛查及随后的专门代谢治疗，早期发现可改善 MTHFR 缺乏症和胱硫醚-β-合成酶缺乏症患者的临床预后和存活率，并在一定程度上改善钴胺素反应性甲基丙二酸血症（MMA）和 cblC 缺乏症患者的临床预后和存活率，而丙酸血症和钴胺素无反应性甲基丙二酸血症患者的获益则不太明显，因为他们的（新生儿）失代偿率、死亡率和长期并发症都很高。

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来源期刊

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”).