Novel biomarkers and age-related metabolite correlations in plasma and dried blood spots from patients with succinic semialdehyde dehydrogenase deficiency

Orphanet Journal of Rare Diseases

Erland Arning¹  Paula Ashcraft¹  Teodoro Bottiglieri¹  Melissa DiBacco²  Phillip L. Pearl²  K. Michael Gibson³  Dana C. Walters³  Xutong Shi³  Trevor Kirby³  Jean-Baptiste Roullet³  Coleman Turgeon⁴  Piero Rinaldo⁴ 

[1] Baylor Scott & White Research Institute, Institute of Metabolic Disease, Dallas, TX, USA;Department of Neurology, Pediatric Neurology, Harvard Medical School and Boston Children’s Hospital, Boston, USA;Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences Building Room 210C, Washington State University, 412 E. Spokane Falls Boulevard, 99202-2131, Spokane, WA, USA;Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, USA;

关键词: Dried blood spots;    Amino acids;    Acylcarnitines;    Creatinine, guanidinoacetate;    Age-dependent correlations;    γ-Hydroxybutyrate (GHB);    γ-Aminobutyrate (GABA);   

DOI  :  10.1186/s13023-020-01522-5

来源: Springer

【 摘 要 】

BackgroundPrevious work has identified age-related negative correlations for γ-hydroxybutyric acid (GHB) and γ-aminobutyric 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.ResultsMetabolites assessed included amino acids (plasma, DBS) and acylcarnitines, creatine, creatinine, and guanidinoacetate (DBS only). Age-related negative correlations for glycine (plasma, DBS) and sarcosine (N-methylglycine, 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).ConclusionsAge-dependent acylcarnitine correlations may represent metabolic compensation responsive to age-related changes in GHB and GABA. Our study highlights novel biomarkers in SSADHD and expands the metabolic pathophysiology of this rare disorder of GABA metabolism.

【 授权许可】

CC BY