Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic sem
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(2020) 15:261
RESEARCH
Open Access
Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency Trevor Kirby1†, Dana C. Walters1†, Xutong Shi1, Coleman Turgeon2, Piero Rinaldo2, Erland Arning3, Paula Ashcraft3, Teodoro Bottiglieri3, Melissa DiBacco4, Phillip L. Pearl4, Jean-Baptiste Roullet1 and K. Michael Gibson1*
Abstract Background: Previous work has identified age-related negative correlations for γ-hydroxybutyric acid (GHB) and γaminobutyric acid (GABA) in plasma of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD). Using plasma and dried blood spots (DBS) collected in an ongoing natural history study, we tested the hypothesis that other biomarkers would follow a similar age-related negative correlation as seen for GHB/GABA. Samples (mixed sex) included: patients (n = 21 unique samples, 1–39.5 yrs) and parallel controls (n = 9 unique samples, 8.4– 34.8 yrs). Archival control data (DBS only; n = 171, 0.5–39.9 yrs) was also included. Results: Metabolites assessed included amino acids (plasma, DBS) and acylcarnitines, creatine, creatinine, and guanidinoacetate (DBS only). Age-related negative correlations for glycine (plasma, DBS) and sarcosine (Nmethylglycine, plasma) were detected, accompanied by elevated proline and decreased levels of succinylacetone, argininosuccinate, formaminoglutamate, and creatinine. Significantly low acylcarnitines were detected in patients across all chain lengths (short-, medium- and long-chain). Significant age-dependent positive correlations for selected acylcarnitines (C6-, C12DC(dicarboxylic)-, C16-, C16:1-, C18:1-, C18:2OH-carnitines) were detected in patients and absent in controls. Receiver operating characteristic (ROC) curves for all binary comparisons revealed argininosuccinate and succinylacetone to be the most discriminating biomarkers (area > 0.92). Conclusions: Age-dependent acylcarnitine correlations may represent metabolic compensation responsive to agerelated changes in GHB and GABA. Our study highlights novel biomarkers in SSADHD and expands the metabolic pathophysiology of this rare disorder of GABA metabolism. Keywords: Dried blood spots, Amino acids, Acylcarnitines, Creatinine, guanidinoacetate, Age-dependent correlations, γ-Hydroxybutyrate (GHB), γ-Aminobutyrate (GABA)
* Correspondence: [email protected] † Trevor Kirby and Dana C. Walters contributed equally to this work. 1 Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences Building Room 210C, Washington State University, 412 E. Spokane Falls Boulevard, Spokane, WA 99202-2131, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the C
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