Abstract
X-linked adrenoleukodystrophy (ALD) is an inherited progressive neurometabolic disease caused by mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids in plasma and tissues. Patients present with heterogeneous clinical manifestations which can include adrenal insufficiency, myelopathy, and/or cerebral demyelination. In the absence of a genotype-phenotype correlation, the clinical outcome of an individual cannot be predicted and currently there are no molecular markers available to quantify disease severity. Therefore, there is an unmet clinical need for sensitive biomarkers to monitor and/or predict disease progression and evaluate therapy efficacy. The increasing amount of biological sample repositories (‘biobanking’) as well as the introduction of newborn screening creates a unique opportunity for identification and evaluation of new or existing biomarkers. Here we summarize and review the many studies that have been performed to identify and improve knowledge surrounding candidate molecular biomarkers for ALD. We also highlight several shortcomings of ALD biomarker studies, which often include a limited sample size, no collection of longitudinal data, and no validation of findings in an external cohort. Nonetheless, these studies have generated a list of interesting biomarker candidates and this review aspires to direct future biomarker research.
Highlights
X-linked adrenoleukodystrophy (ALD) is an inherited, progressive, neurometabolic disease which affects the adrenal cortex, testis, and the central and peripheral nervous system
The authors investigated if measurements of superoxide dismutase (SOD) activity were influenced by long-term storage and freeze-thaw cycles of samples and found that the intraindividual biological variability of plasma SOD was a maximum of 15% over six months, suggesting it is suitable for use as a biomarker [61]
This result contradicts the finding of Petrillo et al, who found no significant difference in SOD activity between myelopathy, cerebral ALD, or control samples [55], this could be due to the difference in assays used in both studies to measure SOD
Summary
X-linked adrenoleukodystrophy (ALD) is an inherited, progressive, neurometabolic disease which affects the adrenal cortex, testis, and the central and peripheral nervous system. It is the most common leukodystrophy with a birth incidence of 1 in 14,700 live births [1]. The clinical manifestations of ALD include adrenal insufficiency, myelopathy, and/or leukodystrophy [8]. The third and most common clinical manifestation of ALD is progressive myelopathy ( referred to as adrenomyeloneuropathy, AMN), which occurs in almost all male ALD patients [10], and 80% of female patients [11,12]
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