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 brainbehavior 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.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…A 2022 report noted that the addition of ALD to the RUSP resulted in published recommendations on the surveillance and care of boys detected by NBS [ 91 ], but challenges remain, which will be addressed with a periodic review of which treatments work, and which do not [ 92 ]. At least three reports on NBS impacts on ALD were published in 2023: a review on the era of NBS with the aim of providing improving case conceptualization, informing prognostic counseling to optimize neuropsychological and mental healthcare for patients and their families [ 93 ]; a report on the impact of NBS on earlier detection and treatment given the large number (29 at the time) of states including ALD on their screening panels [ 94 ]; and a critical review on the impact of NBS on the diagnosis and treatment of male children with adrenal dysfunction reported during the first 10 years of NBS in the USA [ 95 ].…”