Longitudinal metabolomics in dried bloodspots yields profiles informing newborn screening for succinic semialdehyde dehydrogenase deficiency.
Longitudinal metabolomics in dried bloodspots yields profiles informing newborn screening for succinic semialdehyde dehydrogenase deficiency.
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DOI：
10.1002/jmd2.12075
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发表时间：
2020-05-01
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影响因子：
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通讯作者：
Gibson, K Michael
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作者：
Brown, Madalyn;Turgeon, Coleman;Gibson, K Michael
对19种氨基酸、38种酰基肉毒碱和3种肌酸类似物（https：//www.example.com）进行分析，以检验使用当前可用的新生儿筛查方法可以在干血斑（DBS）中鉴定出琥珀酸半醛脱氢酶缺乏症（SSADHD）的假设。clir.mayo.edu研究人群包括17例新生儿后SSADHD DBS（年龄范围为0.8- 38岁;中位数为8.2岁; 10例男性;对照组，129-353例年龄匹配的个体，混合性别）和10例新生儿SSADHD DBS（包括7例患者中3例的第一次和第二次筛选）。新生儿后DBS的低（信息）标记物包括C2-和C4-OH肉毒碱、鸟氨酸、组氨酸和肌酸，无性别差异。对于新生儿DBS，提供信息的标志物包括C2-、C3-、C4-和C4-OH肉毒碱、肌酸和鸟氨酸。其中，只有肌酸表现出随年龄的显着变化，揭示了约4倍的下降。我们的结论是，短链酰基肉毒碱，肌酸和鸟氨酸的定量提供了一个新生儿DBS配置文件作为早期检测SSADHD的第一层筛选工具的潜力。该第一级评价可以使用先前描述的用于相同DBS中的γ-羟基丁酸的第二级液相色谱-串联质谱法容易地验证。需要在更大的人群中对这种第一/第二层筛查方法进行更广泛的评价。
Analyses of 19 amino acids, 38 acylcarnitines, and 3 creatine analogues (https://clir.mayo.edu) were implemented to test the hypothesis that succinic semialdehyde dehydrogenase deficiency (SSADHD) could be identified in dried bloodspots (DBS) using currently available newborn screening methodology. The study population included 17 post-newborn SSADHD DBS (age range 0.8-38years; median, 8.2years; 10 M; controls, 129-353 age-matched individuals, mixed gender) and 10 newborn SSADHD DBS (including first and second screens from 3 of 7 patients). Low (informative) markers in post-newborn DBS included C2- and C4-OH carnitines, ornithine, histidine and creatine, with no gender differences. For newborn DBS, informative markers included C2-, C3-, C4- and C4-OH carnitines, creatine and ornithine. Of these, only creatine demonstrated a significant change with age, revealing an approximate 4-fold decrease. We conclude that quantitation of short-chain acylcarnitines, creatine, and ornithine provides a newborn DBS profile with potential as a first tier screening tool for early detection of SSADHD. This first tier evaluation can be readily verified using a previously described second tier liquid chromatography-tandem mass spectrometry method for gamma-hydroxybutyric acid in the same DBS. More extensive evaluation of this first/second tier screening approach is needed in a larger population.