Defining diagnostic cutoffs in neurological patients for serum very long chain fatty acids (VLCFA) in genetically confirmed X-Adrenoleukodystrophy

X-linked Adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene resulting in the accumulation of very long chain fatty acids (VLCFA). X-ALD is the most common peroxisomal disorder with adult patients (male and female) presenting with progressive spastic paraparesis with bladder distur...

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Bibliographic Details
Published in:Scientific reports 2020-09, Vol.10 (1), p.15093-15093, Article 15093
Main Authors: Rattay, Tim W, Rautenberg, Maren, Söhn, Anne S, Hengel, Holger, Traschütz, Andreas, Röben, Benjamin, Hayer, Stefanie N, Schüle, Rebecca, Wiethoff, Sarah, Zeltner, Lena, Haack, Tobias B, Cegan, Alexander, Schöls, Ludger, Schleicher, Erwin, Peter, Andreas
Format: Article
Language:English
Subjects:
Adrenoleukodystrophy - blood
Adrenoleukodystrophy - diagnosis
Adult
Aged
Astrocytes - pathology
ATP-Binding Cassette Transporters - genetics
Biomarkers - blood
Fatty Acids - blood
Female
Humans
Male
Middle Aged
Mutation - genetics
Sensitivity and Specificity
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Summary:X-linked Adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene resulting in the accumulation of very long chain fatty acids (VLCFA). X-ALD is the most common peroxisomal disorder with adult patients (male and female) presenting with progressive spastic paraparesis with bladder disturbance, sensory ataxia with impaired vibration sense, and leg pain. 80% of male X-ALD patients have an adrenal failure, while adrenal dysfunction is rare in women with X-ALD. The objective of this study was to define optimal serum VLCFA cutoff values in patients with X-ALD-like phenotypes for the differentiation of genetically confirmed X-ALD and Non-X-ALD individuals. Three groups were included into this study: a) X-ALD cases with confirmed ABCD1 mutations (n = 34) and two Non-X-ALD cohorts: b) Patients with abnormal serum VCLFA levels despite negative testing for ABCD1 mutations (n = 15) resulting from a total of 1,953 VLCFA tests c) Phenotypically matching patients as Non-X-ALD controls (n = 104). Receiver operating curve analysis was used to optimize VLCFA cutoff values, which differentiate patients with genetically confirmed X-ALD and Non-X-ALD individuals. The serum concentration of C26:0 was superior to C24:0 for the detection of X-ALD. The best differentiation of Non-X-ALD and X-ALD individuals was obtained with a cutoff value of 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-71248-8