Presentation (CTI)

OBJECTIVES: Metachromatic leukodystrophy (MLD) is an ultra-rare, fatal inherited neurodegenerative lysosomal storage disease characterized by toxic sulfatide accumulation, resulting in progressive motor and cognitive decline. Disease management requires complex multidisciplinary care. This study systematically synthesized recent global evidence on the burden of illness associated with MLD.
METHODS: An AI-assisted targeted literature review was conducted using EasySLR. Structured searches of MEDLINE and Embase were performed via Embase.com to identify English-language studies published from 2016 onward, while conference abstracts were limited to 2023 onward. Studies were screened according to predefined eligibility criteria.
RESULTS: Of 209 records identified, 42 studies underwent full-text review, and eight observational studies met the inclusion criteria. Studies were conducted in the United States (n=3), France (n=1), Germany (n=1), and multinational cohorts across the United Kingdom, Ireland, Belgium, the Netherlands, and Norway (n=3). In advanced untreated late infantile (LI) and early juvenile (EJ) MLD, almost all patients experienced severe spasticity, dysphagia, and loss of voluntary movement, with wheelchair dependence (84.6% to 100%) and enteral feeding (46.2% to 100%) frequently required. Healthcare utilization included approximately one inpatient admission and up to 29.6 outpatient visits annually, largely driven by diagnostic evaluations and supportive care. Real-world evidence showed annual medical costs increased by approximately US$5,600 per year following diagnosis, primarily because of home nursing services. Estimated lifetime family income loss ranged from US$348,041 for LI to US$423,304 for EJ disease. Between 76.5% and 90% of caregivers modified employment or exited the workforce. Caregivers also reported substantially reduced health-related quality of life, with up to 80% experiencing chronic anxiety, depression, and significant physical strain.
CONCLUSIONS: Untreated MLD imposes a profound clinical, economic, and societal burden on patients, caregivers, and healthcare systems. These findings provide essential benchmark evidence to support future health technology assessments and evaluations of emerging disease-modifying therapies.