| Quantitative acylcarnitine profiling in peripheral blood mononuclear cells using in vitro loading with palmitic and 2-oxoadipic acids: biochemical confirmation of fatty acid oxidation and organic acid disorders. | |
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MedLine Citation:
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PMID: 16183823 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Organic acid (OAD) and fatty acid oxidation disorders (FAOD) are inborn errors of metabolism often presenting with life-threatening metabolic decompensation followed by (irreversible) organ failure, and even death during catabolic state. Most of these diseases are considered as treatable, and metabolic decompensations can be avoided by early diagnosis and start of therapy. Confirmation of suspected diagnosis currently relies on enzymatic and mutation analyses and in vitro loading of palmitic acid in human skin fibroblast cultures. Furthermore, in some cases potentially life-threatening in vivo loading or fasting tests are still performed. In this study, we established a standardized in vitro loading test in peripheral blood mononuclear cells (PBMC) that allows reliable biochemical confirmation of a suspected diagnosis within 1 week. Patients with confirmed diagnosis of short-, medium-, very-long-chain, and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencies, methylmalonic, propionic, isovaleric acidurias, and glutaric aciduria type I were included in the study. PBMC, isolated from heparinized venous blood samples of these individuals were incubated for 5 days with palmitic acid or 2-oxoadipic acid (glutaric aciduria type I), respectively, and quantitative acylcarnitine profiling was subsequently performed in supernatants using electrospray ionization tandem mass spectrometry. All patients were clearly identified, including those with mild biochemical phenotypes who, in particular, are at risk to be missed under balanced metabolic conditions. In glutaric aciduria type I, the same results were also obtained using lymphoblasts. In conclusion, our assay allows biochemical confirmation of a number of FAOD and OAD and could easily be implemented into the confirmatory diagnostic work-up. |
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Authors:
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Andrea Schulze-Bergkamen; Jürgen G Okun; Ute Spiekerkötter; Martin Lindner; Dorothea Haas; Dirk Kohlmüller; Ertan Mayatepek; Henning Schulze-Bergkamen; Cheryl R Greenberg; Johannes Zschocke; Georg F Hoffmann; Stefan Kölker |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-09-23 |
Journal Detail:
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Title: Pediatric research Volume: 58 ISSN: 0031-3998 ISO Abbreviation: Pediatr. Res. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-31 Completed Date: 2006-01-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 873-80 Citation Subset: IM |
Affiliation:
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Department of General Pediatrics, University Children's Hospital Heidelberg, 69120 Heidelberg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipic Acids
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administration & dosage* Carnitine / analogs & derivatives*, blood Child Child, Preschool Female Humans Infant Male Mass Spectrometry Metabolism, Inborn Errors / blood, diagnosis* Monocytes / metabolism* Palmitic Acid / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Adipic Acids; 0/acylcarnitine; 3184-35-8/alpha-ketoadipic acid; 541-15-1/Carnitine; 57-10-3/Palmitic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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