Infants with biliary atresia exhibit an altered amino acid profile in their newborn screening.

IF 3.5 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Metabolomics Pub Date : 2024-10-05 DOI:10.1007/s11306-024-02175-2

Marie Uecker, Cornelia Prehn, Nils Janzen, Jerzy Adamski, Gertrud Vieten, Claus Petersen, Joachim F Kuebler, Omid Madadi-Sanjani, Christian Klemann

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Abstract

Introduction: Biliary atresia (BA) is a rare progressive neonatal cholangiopathy with unknown pathophysiology and time of onset. Newborn Screening (NBS) in Germany is routinely performed in the first days of life to identify rare congenital diseases utilizing dried blood spot (DBS) card analyses. Infants with biliary atresia (BA) are known to have altered amino acid profiles (AAP) at the time point of diagnosis, but it is unclear whether these alterations are present at the time point of NBS.

Objectives: We aimed to analyze amino acid profiles in NBS-DBS of infants with Biliary Atresia.

Methods: Original NBS-DBS cards of 41 infants who were later on diagnosed with BA were retrospectively obtained. NBS-DBS cards from healthy newborns (n = 40) served as controls. In some BA infants (n = 14) a second DBS card was obtained at time of Kasai surgery. AAP in DBS cards were analyzed by targeted metabolomics.

Results: DBS metabolomics in the NBS of at that time point seemingly healthy infants later diagnosed with BA revealed significantly higher levels of Methionine (14.6 ± 8.6 μmol/l), Histidine (23.5 ± 50.3 μmol/l), Threonine (123.9 ± 72.8 μmol/l) and Arginine (14.1 ± 11.8 μmol/l) compared to healthy controls (Met: 8.1 ± 2.6 μmol/l, His: 18.6 ± 10.1 μmol/l, Thr: 98.1 ± 34.3 μmol/l, Arg: 9.3 ± 6.6 μmol/l). Methionine, Arginine and Histidine showed a further increase at time point of Kasai procedure. No correlation between amino acid levels and clinical course was observed.

Conclusion: Our data demonstrate that BA patients exhibit an altered AAP within 72 h after birth, long before the infants become symptomatic. This supports the theory of a prenatal onset of the disease and, thus, the possibility of developing a sensitive and specific NBS. Methionine might be particularly relevant due to its involvement in glutathione metabolism. Further investigation of AAP in BA may help in understanding the underlying pathophysiology.

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患有胆道闭锁的婴儿在新生儿筛查中表现出氨基酸谱的改变。

导言：胆道闭锁（BA）是一种罕见的进行性新生儿胆道病，其病理生理和发病时间尚不清楚。在德国，新生儿筛查（NBS）通常在婴儿出生后的头几天进行，利用干血斑卡（DBS）分析来确定罕见的先天性疾病。众所周知，患有胆道闭锁（BA）的婴儿在确诊时会出现氨基酸谱（AAP）改变，但目前还不清楚这些改变是否会在 NBS 时出现：我们旨在分析胆道闭锁婴儿 NBS-DBS 中的氨基酸谱：方法：我们回顾性地获得了41名后来被诊断为胆道闭锁的婴儿的原始NBS-DBS卡。健康新生儿（40 人）的 NBS-DBS 卡作为对照。一些 BA 婴儿（n = 14）在接受 Kasai 手术时获得了第二张 DBS 卡。通过靶向代谢组学分析 DBS 卡中的 AAP：结果：当时看似健康的婴儿后来被诊断为 BA，其 NBS 中的 DBS 代谢组学显示蛋氨酸（14.6 ± 8.6 μmol/l）、组氨酸（23.5 ± 50.3 μmol/l）、苏氨酸（123.9 ± 72.8 μmol/l）和精氨酸（14.1 ± 11.8 μmol/l）与健康对照组相比（Met：8.1 ± 2.6 μmol/l；His：18.6 ± 10.1 μmol/l；Thr：98.1 ± 34.3 μmol/l；Arg：9.3 ± 6.6 μmol/l）。甲硫氨酸、精氨酸和组氨酸在进行 Kasai 程序时进一步增加。氨基酸水平与临床病程无相关性：我们的数据表明，BA 患者在出生后 72 小时内，也就是在婴儿出现症状之前，AAP 就已经发生了改变。这支持了产前发病的理论，因此有可能开发出一种敏感而特异的 NBS。由于蛋氨酸参与谷胱甘肽的代谢，因此可能与该病特别相关。对 BA 中 AAP 的进一步研究可能有助于了解潜在的病理生理学。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Metabolomics 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.80%

发文量

审稿时长

2 months

期刊介绍： Metabolomics publishes current research regarding the development of technology platforms for metabolomics. This includes, but is not limited to: metabolomic applications within man, including pre-clinical and clinical pharmacometabolomics for precision medicine metabolic profiling and fingerprinting metabolite target analysis metabolomic applications within animals, plants and microbes transcriptomics and proteomics in systems biology Metabolomics is an indispensable platform for researchers using new post-genomics approaches, to discover networks and interactions between metabolites, pharmaceuticals, SNPs, proteins and more. Its articles go beyond the genome and metabolome, by including original clinical study material together with big data from new emerging technologies.