Diagnosis of X-linked adrenoleukodystrophy in blood leukocytes

Objectives:Our aim was to replace cultured skin fibroblasts in the diagnosis of X-linked adrenoleukodystrophy (X-ALD) by peripheral blood cells.Design and methods:Very long chain fatty acids (VLCFAs) were analyzed in leukocytes from X-ALD patients, heterozygotes, and controls using gas chromatography–mass spectrometry (GC–MS). Immunofluorescence for adrenoleukodystrophy protein (ALDP) was performed in mononuclear blood cell preparations of X-ALD patients known to be ALDP negative in fibroblasts, heterozygote relatives of these patients, and controls.Results:All X-ALD patients were distinguishable from controls by VLCFA analysis in leukocytes. 91.7% of heterozygotes were identified by combined VLCFA analysis in leukocytes and plasma. All patients investigated lacked ALDP immunoreactivity in mononuclear cells, while heterozygotes showed mosaic patterns of positive and negative cells.Conclusion:Determination of VLCFAs by GC–MS in combination with ALDP immunofluorescence in peripheral blood cells provides a fast and minimally invasive diagnostic method for X-ALD, which, in contrast to plasma analysis, is independent of alimentary influences. Notably, joint evaluation of leukocytes and plasma considerably improves the identification of heterozygotes.