Dataset Information

Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.

ABSTRACT: The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.

SUBMITTER: Dezfouli M

PROVIDER: S-EPMC7090021 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.

Dezfouli Mahya M Bergström Sofia S Skattum Lillemor L Abolhassani Hassan H Neiman Maja M Torabi-Rahvar Monireh M Franco Jarava Clara C Martin-Nalda Andrea A Ferrer Balaguer Juana M JM Slade Charlotte A CA Roos Anja A Fernandez Pereira Luis M LM López-Trascasa Margarita M Gonzalez-Granado Luis I LI Allende-Martinez Luis M LM Mizuno Yumi Y Yoshida Yusuke Y Friman Vanda V Lundgren Åsa Å Aghamohammadi Asghar A Rezaei Nima N Hernández-Gonzalez Manuel M von Döbeln Ulrika U Truedsson Lennart L Hara Toshiro T Nonoyama Shigeaki S Schwenk Jochen M JM Nilsson Peter P Hammarström Lennart L

Frontiers in immunology 20200317

The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part ...[more]

PMID: 32256498

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Project description:Some success in identifying acyl-CoA dehydrogenase (ACAD) deficiencies before they are symptomatic has been achieved through tandem mass spectrometry. However, there has been several challenges that need to be confronted, including excess false positives, the occasional false negatives and indicators selection. To select ideal indicators and evaluate their performance for identifying ACAD deficiencies, data from 352,119 newborn babies, containing 20 cases, were used in this retrospective study. A total of three new ratios, C4/C5DC+C6-OH, C8/C14:1, and C14:1/C16-OH, were selected from 43 metabolites. Around 903 ratios derived from pairwise combinations of all metabolites via multivariate logistic regression analysis were used. In the current study, the regression analysis was performed to identify short chain acyl-CoA dehydrogenase (SCAD) deficiency, medium chain acyl-CoA dehydrogenase (MCAD) deficiency, and very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. In both model-building and testing data, the C4/C5DC+C6-OH, C8/C14:1 and C14:1/C16-OH were found to be better indicators for SCAD, MCAD and VLCAD deficiencies, respectively, compared to [C4, (C4, C4/C2)], [C8, (C6, C8, C8/C2, C4DC+C5-OH/C8:1)], and [C14:1, (C14:1, C14:1/C16, C14:1/C2)], respectively. In addition, 22 mutations, including 5 novel mutations and 17 reported mutations, in ACADS, ACADM, and ACADL genes were detected in 20 infants with ACAD deficiency by using high-thorough sequencing based on target capture. The pathogenic mutations of c.1031A > G in ACADS, c.449_452delCTGA in ACADM and c.1349G > A in ACADL were found to be hot spots in Suzhou patients with SCAD, MCAD, and VLCAD, respectively. In conclusion, we had identified three new ratios that could improve the performance for ACAD deficiencies compared to the used indicators. We considered to utilize C4/C5DC+C6-OH, C8/C14:1, and C14:1/C16-OH as primary indicators for SCAD, MCAD, and VLCAD deficiency, respectively, in further expanded newborn screening practice. In addition, the spectrum of mutations in Suzhou population enriches genetic data of Chinese patients with one of ACAD deficiencies.

Dataset Information

Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.

Publications

Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.

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