BACKGROUND: The therapeutic scenario of X-linked adrenoleukodystrophy (X-ALD) is rapidly changing. Whereas the disease is well characterized in males, the condition remains to be fully clarified in women carrying ABCD1 variants. Specifically, data on clinical progression are needed, in order to recommend any appropriate management. Objective of this study is to outline the natural history of a cohort of untreated ABCD1 heterozygous female carries.
METHODS: Longitudinal data from a single-center population of 60 carriers were retrospectively reviewed. Demographics, anthropometrics, serum very-long chain fatty acids (VLCFA) levels, clinical parameters and the Adult ALD Clinical Score (AACS) were collected from every recorded visits in a 7 years long period and analyzed to define the phenotype modifications, to determine factors associated with clinical features, to estimate the annual progression rate and the subsequent sample size for interventional trials.
RESULTS: 32 patients were eligible for the study, 59.4% was symptomatic at baseline. Clinical severity worsens with age that increases risk of symptoms onset, being the cut-off of 41 years crucial for phenoconversion. VLCFA levels were not predictive and did not change over time. Symptomatic carriers were followed-up for 3.45±2.1 years. AACS score increased with an annual rate of 0.24 points. The estimated sample size for 30% reduction in annual progression at 80% power was 272.
CONCLUSIONS: This study provides data on the natural disease progression of untreated ABCD1 heterozygous female carriers, demonstrating the relevance of aging. The estimated annual increase of the AACS score will turn to be useful for future interventional studies. This article is protected by copyright. All rights reserved.