Scholars@Duke publication: A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency.

A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency.

Publication , Journal Article

Young, SP; Matern, D; Gregersen, N; Stevens, RD; Bali, D; Liu, H-M; Koeberl, DD; Millington, DS

Published in: Clin Chim Acta

November 2003

BACKGROUND: Homozygosity and compound heterozygosity for the short chain acyl-CoA dehydrogenase (SCAD) gene sequence variants 625G-->A and 511C-->T are associated with ethylmalonic aciduria (EMA), a biochemical indicator of SCAD deficiency. The clinical and biochemical implications of these variants are not fully understood. The effect of these variants on the accumulation of butyrylcarnitine by fibroblasts in culture was studied. METHODS: In vitro acylcarnitine profiling in fibroblasts was carried out using [U-13C]-labeled or unlabeled palmitate in the presence of excess L-carnitine, with or without a medium chain acyl-CoA dehydrogenase (MCAD) inhibitor. Acylcarnitines were analyzed using tandem mass spectrometry. 625G/625G (wild type), 625G/625A and 625A/625A (variant) control fibroblasts were compared with fibroblasts from patients homozygous for inactivating SCAD mutations (SCAD deficient) and from patients with EMA who were homozygous or compound heterozygous for the SCAD variants. RESULTS: Variant control and patient fibroblasts accumulated moderate amounts of butyrylcarnitine compared with wild-type controls and in contrast to the significant amount of butyrylcarnitine accumulated by SCAD deficient fibroblasts, regardless of incubation conditions. CONCLUSIONS: Moderately reduced SCAD activity associated with SCAD variants can be detected using in vitro acylcarnitine profiling methods, which may be used as an indirect measure of SCAD activity.

Duke Scholars

Author Sarah Phyllis Young Pediatrics, Medical Genetics

Author Robert David Stevens Medicine, Endocrinology, Metabolism, and Nutrition

Author Deeksha Sarihyan Bali Pediatrics, Medical Genetics

Author Dwight D. Koeberl Pediatrics, Medical Genetics

Author David Stuart Millington Pediatrics, Medical Genetics

Published In

Clin Chim Acta

DOI

10.1016/j.cccn.2003.07.006

ISSN

0009-8981

Publication Date

November 2003

Volume

337

Issue

1-2

Start / End Page

103 / 113

Location

Netherlands

Related Subject Headings

Spiro Compounds
Spectrometry, Mass, Electrospray Ionization
Sensitivity and Specificity
Polymorphism, Genetic
Palmitoylcarnitine
Palmitic Acid
Mutation, Missense
Malonates
Humans
Homozygote

Citation

APA

Chicago

ICMJE

MLA

NLM

Young, S. P., Matern, D., Gregersen, N., Stevens, R. D., Bali, D., Liu, H.-M., … Millington, D. S. (2003). A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency. Clin Chim Acta, 337(1–2), 103–113. https://doi.org/10.1016/j.cccn.2003.07.006

Young, Sarah P., Dietrich Matern, Niels Gregersen, Robert D. Stevens, Deeksha Bali, Hui-Ming Liu, Dwight D. Koeberl, and David S. Millington. “A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency.” Clin Chim Acta 337, no. 1–2 (November 2003): 103–13. https://doi.org/10.1016/j.cccn.2003.07.006.

Young SP, Matern D, Gregersen N, Stevens RD, Bali D, Liu H-M, et al. A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency. Clin Chim Acta. 2003 Nov;337(1–2):103–13.

Young, Sarah P., et al. “A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency.” Clin Chim Acta, vol. 337, no. 1–2, Nov. 2003, pp. 103–13. Pubmed, doi:10.1016/j.cccn.2003.07.006.

Young SP, Matern D, Gregersen N, Stevens RD, Bali D, Liu H-M, Koeberl DD, Millington DS. A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency. Clin Chim Acta. 2003 Nov;337(1–2):103–113.