Improved analysis of C26:0-lysophosphatidylcholine in dried-blood spots via negative ion mode HPLC-ESI-MS/MS for X-linked adrenoleukodystrophy newborn screening.

Abstract

BACKGROUND:

X-linked adrenoleukodystrophy (X-ALD) is the most common human peroxisomal disorder, and is caused by mutations in the peroxisomal transmembrane ALD protein (ALDP, ABCD1). The biochemical defect associated with X-ALD is an accumulation of very long-chain fatty acids (VLCFA, e.g. C24:0 and C26:0), which has been shown to result in the accumulation of C26:0-lysophosphatidylcholine (C26:0-LPC).

METHODS:

We describe the analysis of C26:0-LPC in dried-blood spots (DBS) using a rapid (30 min) and simple extraction procedure, isocratic HPLC resolution of LPC, and structure-specific analysis via negative ion mode tandem mass spectrometry.

RESULTS:

In putative normal DBS specimens from newborns (N=223) C26:0-LPC was 0.09±0.03 μmol/l whole blood, while in peroxisomal biogenesis disorder (including X-ALD) patients (N=28) C26:0-LPC was 1.13±0.67 μmol/l whole blood. Both multiple reaction monitoring and a neutral loss scan (225.1 Da) analysis of DBS were used to analyze LPC.

CONCLUSIONS:

Compared to a previous report of C26:0-LPC analysis in DBS, the method described here is simpler, faster, and more structure-specific for LPC with C26:0 acyl chains.

• Authors: Christopher A Haynes, Víctor R De Jesús
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 413 Issue 15-16 Pg. 1217-21 (Aug 16 2012) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 22503909 (Publication Type: Evaluation Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Published by Elsevier B.V.

Chemical References

• Lysophosphatidylcholines

Topics

• Adrenoleukodystrophy (blood, diagnosis, genetics)
• Chromatography, High Pressure Liquid (methods)
• Dried Blood Spot Testing (methods)
• Humans
• Infant, Newborn
• Lysophosphatidylcholines (blood)
• Neonatal Screening
• Peroxisomal Disorders (blood)
• Reference Values
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tandem Mass Spectrometry