Evaluation of c26:0-Lyso-Phosphatidylcholine Levels in X-Linked Adrenoleukodystrophy: Diagnosis and Biochemical
Gilian Guerreiro1, Marion Deon1, Graziela Becker1
1Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
Introduction:
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, caused by ABCD1 mutations that impair very long-chain fatty acid (VLCFA) degradation, leading to progressive neurological damage and adrenal insufficiency. C26:0-Lysophosphatidylcholine (C26:0-Lyso-PC) has emerged as a robust biomarker for X-ALD and a candidate for newborn screening programs.
Objectives:
The objective of this study is to standardize and validate C26:0-Lyso-PC quantification by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and evaluate its diagnostic accuracy in high-risk populations.
Design And Methods:
Reference values were established from 25 healthy controls and compared with five confirmed X-ALD cases (one cerebral childhood form, three heterozygous women and one asymptomatic male). Additionally, 64 DBS samples from individuals at high risk for inborn errors of metabolism (IEM) were tested. Plasma VLCFA were quantified by gas chromatography-mass spectrometry (GC/MS).
Results:
Control C26:0-Lyso-PC values ranged from 0.13 to 0.25 μg/mL (mean = 0.19 μg/mL). All X-ALD patients exhibited elevated concentrations (0.377-0.787 μg/mL). Among samples from patients at high risk for disease, four were abnormal-two consistent with X-ALD and two with other peroxisomal disorders. Strong correlations were observed between C26:0-Lyso-PC and plasma C26:0 (r = 0.952, p < 0.001) and the C26:0/C22:0 ratio (r = 0.801, p < 0.05). The method demonstrated high reproducibility (intra-assay CV = 8.6% and interassay CV = 12.8%).
Conclusions:
C26:0-Lyso-PC measurement in DBS by LC-MS/MS is a rapid, sensitive and reproducible alternative to plasma VLCFA analysis, enabling reliable discrimination of X-ALD and other peroxisomal disorders. These findings support its integration into targeted and population-based screening to allow presymptomatic diagnosis, early intervention and genetic counselling.
