Document Detail

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.
MedLine Citation:
PMID:  16183823     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-09-23
Journal Detail:
Title:  Pediatric research     Volume:  58     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-31     Completed Date:  2006-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  873-80     Citation Subset:  IM    
Department of General Pediatrics, University Children's Hospital Heidelberg, 69120 Heidelberg, Germany.
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MeSH Terms
Adipic Acids / administration & dosage*
Carnitine / analogs & derivatives*,  blood
Child, Preschool
Mass Spectrometry
Metabolism, Inborn Errors / blood,  diagnosis*
Monocytes / metabolism*
Palmitic Acid / administration & dosage*
Reg. No./Substance:
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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