دورية أكاديمية
Dicarboxylic acylcarnitine biomarkers in peroxisome biogenesis disorders.
| العنوان: | Dicarboxylic acylcarnitine biomarkers in peroxisome biogenesis disorders. |
|---|---|
| المؤلفون: | Wangler MF; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States of America; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States of America., Lesko B; Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN 46202, United States of America., Dahal R; Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN 46202, United States of America., Jangam S; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States of America; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States of America., Bhadane P; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States of America; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States of America., Wilson TE; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America., McPheron M; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America., Miller MJ; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America. Electronic address: majamill@iu.edu. |
| المصدر: | Molecular genetics and metabolism [Mol Genet Metab] 2023 Nov; Vol. 140 (3), pp. 107680. Date of Electronic Publication: 2023 Aug 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Academic Press Country of Publication: United States NLM ID: 9805456 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-7206 (Electronic) Linking ISSN: 10967192 NLM ISO Abbreviation: Mol Genet Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Orlando, FL : Academic Press, c1998- |
| مواضيع طبية MeSH: | Adrenoleukodystrophy*/diagnosis , Adrenoleukodystrophy*/genetics , Peroxisomal Disorders*/diagnosis , Peroxisomal Disorders*/genetics, Infant, Newborn ; Humans ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Biomarkers ; ATPases Associated with Diverse Cellular Activities ; Membrane Proteins/genetics ; Membrane Proteins/metabolism |
| مستخلص: | The peroxisome is an essential eukaryotic organelle with diverse metabolic functions. Inherited peroxisomal disorders are associated with a wide spectrum of clinical outcomes and are broadly divided into two classes, those impacting peroxisome biogenesis (PBD) and those impacting specific peroxisomal factors. Prior studies have indicated a role for acylcarnitine testing in the diagnosis of some peroxisomal diseases through the detection of long chain dicarboxylic acylcarnitine abnormalities (C16-DC and C18-DC). However, there remains limited independent corroboration of these initial findings and acylcarnitine testing for peroxisomal diseases has not been widely adopted in clinical laboratories. To explore the utility of acylcarnitine testing in the diagnosis of peroxisomal disorders we applied a LC-MS/MS acylcarnitine method to study a heterogenous clinical sample set (n = 598) that included residual plasma specimens from nineteen patients with PBD caused by PEX1 or PEX6 deficiency, ranging in severity from lethal neonatal onset to mild late onset forms. Multiple dicarboxylic acylcarnitines were significantly elevated in PBD patients including medium to long chain (C8-DC to C18-DC) species as well as previously undescribed elevations of malonylcarnitine (C3-DC) and very long chain dicarboxylic acylcarnitines (C20-DC and C22-DC). The best performing plasma acylcarnitine biomarkers, C20-DC and C22-DC, were detected at elevated levels in 100% and 68% of PBD patients but were rarely elevated in patients that did not have a PBD. We extended our analysis to residual newborn screening blood spot cards and were able to detect dicarboxylic acylcarnitine abnormalities in a newborn with a PBD caused by PEX6 deficiency. Similar to prior studies, we failed to detect substantial dicarboxylic acylcarnitine abnormalities in blood spot cards from patients with x-linked adrenoleukodystrophy (x-ald) indicating that these biomarkers may have utility in quickly narrowing the differential diagnosis in patients with a positive newborn screen for x-ald. Overall, our study identifies widespread dicarboxylic acylcarnitine abnormalities in patients with PBD and highlights key acylcarnitine biomarkers for the detection of this class of inherited metabolic disease. Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest. (Copyright © 2023 Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | R01 NS107733 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: Acylcarnitine biomarkers in peroxisomal disease; Acylcarnitine profile analysis; LC-MS/MS acylcarnitine analysis; Newborn screening acylcarnitine; X-linked adrenoleukodystrophy |
| المشرفين على المادة: | 0 (acylcarnitine) 0 (Biomarkers) EC 3.6.4.- (PEX1 protein, human) EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities) 0 (Membrane Proteins) EC 3.6.4.- (PEX6 protein, human) |
| SCR Disease Name: | Peroxisome biogenesis disorders |
| تواريخ الأحداث: | Date Created: 20230811 Date Completed: 20231114 Latest Revision: 20240222 |
| رمز التحديث: | 20240222 |
| مُعرف محوري في PubMed: | PMC10840807 |
| DOI: | 10.1016/j.ymgme.2023.107680 |
| PMID: | 37567036 |
| قاعدة البيانات: | MEDLINE |
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