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