Humanistic Burden of Adrenoleukodystrophy: A Systematic Review

OBJECTIVES: Adrenoleukodystrophy (ALD) is an X-linked genetic condition resulting from the abnormal metabolism of the very long chain fatty acids, with an estimated birth incidence of 1 in 14,700. The disease impacts patients through a range of physical, emotional, and social factors, all contributing to poor quality of life. This systematic review aimed to identify and summarize quality of life (QoL) outcomes in ALD.

METHODS: Key biomedical databases (EMBASE^®, MEDLINE^®) were searched from database inception to June 2024. The search terms included different combinations of ALD and QoL measures. Each publication was reviewed by two independent reviewers with conflicts resolved by a third reviewer.

RESULTS: A total six of 123 screened publications were included (Europe=3, US=1, UK=1, Europe/US=1). The sample size of ALD patients ranged from 46-180, while the mean age ranged from 42.3-51.2 years. The majority of the studies used the Short Form Health Survey (SF-36) to assess QoL (n=4), whereas one study each used SF-Qualiveen and a survey questionnaire to report QoL data. Patients with ALD who experienced gait difficulties, urinary, and bowel symptoms reported a decline in their QoL, with a significant correlation observed between postural body sway and various domains of the SF-36: physical functioning (p<0.001), general health (p=0.002), energy/fatigue (p=0.004), pain (p=0.007). Across two studies, symptomatic patients reported higher mean scores in all SF-36 domains compared to asymptomatic patients indicating poor QoL, with significant differences reported in physical health (17.06 vs. 35.46, p<0.05) and physical functioning (18.03 vs. 33.15, p<0.05) domain. In another study, significant findings were reported across all subscales (p<0.001), except for mental health component.

CONCLUSIONS: Symptomatic ALD patients present with physical and psychological comorbidities significantly impacting their QoL, particularly physical disability. The findings highlight the necessity of developing advanced treatment options to enhance the QoL of ALD patients.