The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review

Eur J Med Res. 2024 Mar 18;29(1):181. doi: 10.1186/s40001-024-01771-1.


Background: Metachromatic leukodystrophy (MLD; OMIM 250100 and 249900) is a rare lysosomal storage disease caused by deficient arylsulfatase A activity, leading to accumulation of sulfatides in the nervous system. This systematic literature review aimed to explore the effect of MLD on the lives of patients.

Methods: The Ovid platform was used to search Embase, MEDLINE, and the Cochrane Library for articles related to the natural history, clinical outcomes, and burden of illness of MLD; congress and hand searches were performed using 'metachromatic leukodystrophy' as a keyword. Of the 531 publications identified, 120 were included for data extraction following screening. A subset of findings from studies relating to MLD natural history and burden of illness (n = 108) are presented here.

Results: The mean age at symptom onset was generally 16-18 months for late-infantile MLD and 6-10 years for juvenile MLD. Age at diagnosis and time to diagnosis varied widely. Typically, patients with late-infantile MLD presented predominantly with motor symptoms and developmental delay; patients with juvenile MLD presented with motor, cognitive, and behavioral symptoms; and patients with adult MLD presented with cognitive symptoms and psychiatric and mood disorders. Patients with late-infantile MLD had more rapid decline of motor function over time and lower survival than patients with juvenile MLD. Commonly reported comorbidities/complications included ataxia, epilepsy, gallbladder abnormalities, incontinence, neuropathy, and seizures.

Conclusions: Epidemiology of MLD by geographic regions, quantitative cognitive data, data on the differences between early- and late-juvenile MLD, and humanistic or economic outcomes were limited. Further studies on clinical, humanistic (i.e., quality of life), and economic outcomes are needed to help inform healthcare decisions for patients with MLD.

Keywords: Burden of illness; Lysosomal storage disease; MLD; Metachromatic leukodystrophy; Natural history; Systematic literature review.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • Adult
  • Cost of Illness
  • Humans
  • Leukodystrophy, Metachromatic* / complications
  • Leukodystrophy, Metachromatic* / diagnosis
  • Leukodystrophy, Metachromatic* / epidemiology
  • Quality of Life