Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening

Abstract

X-linked adrenoleukodystrophy (ALD) is a rare inherited neurological disorder that poses considerable challenges for clinical management throughout the lifespan. Although males are generally more severely affected than females, the time course and presentation of clinical symptoms are otherwise difficult to predict. Opportunities to improve outcomes for individuals with ALD are rapidly expanding due to the introduction of newborn screening programs for this condition and an evolving treatment landscape. The aim of this comprehensive review is to synthesize current knowledge regarding the neurocognitive and mental health effects of ALD. This review provides investigators and clinicians with context to improve case conceptualization, inform prognostic counseling, and optimize neuropsychological and mental health care for patients and their families. Results highlight key predictive factors and brain-behavior relationships associated with the diverse manifestations of ALD. The review also discusses considerations for endpoints within clinical trials and identifies gaps to address in future research.

Keywords: adrenal insufficiency; adrenomyeloneuropathy; assessment; behavior; neuropsychology; psychiatric.

Figure 1.

A) T2 axial FLAIR brain MRI showing a small region of demyelination in the splenium of the corpus callosum (Loes score = 1). This patient with CCALD showed no clinical deficits on neuropsychological testing when examined prior to treatment at 7.4 years of age. B) T2 axial FLAIR brain MRI from another patient with CCALD showing a larger region of demyelination involving parietal-occipital white matter (Loes score = 7). This patient showed clinical neuropsychological deficits including slowed processing speed and moderate visual-motor impairment when evaluated prior to treatment at 7.9 years of age.