OBJECTIVES: Metachromatic leukodystrophy (MLD) is a rare inherited disorder affecting the central nervous system. MLD is classified into four main clinical subtypes based on age of onset: late-infantile, early- and late-juvenile, and adult. This research reviewed the symptoms and impacts of the three paediatric clinical subtypes. Conceptual models representing these were developed to facilitate understanding of outcomes of importance in these patient and caregiver populations.

METHODS: A systematic search was conducted in PubMed and complemented using Google Scholar. N=256 articles were identified, of which n=13 met inclusion/exclusion criteria for relevance.

RESULTS: Studies indicate that patients with late-infantile MLD experience faster decline from initial symptom(s) to first functional loss. Late-infantile MLD is characterised by atypical development from 6 to 18 months of age followed by progressive regression in motor skills. Multiple studies report gait-related changes or frequent falls as early manifestations of the disease. Other symptoms in late-infantile MLD include deterioration in vision and speech, muscle weakness and difficulty eating and swallowing.

Research literature also indicates that patients with early- and late- juvenile MLD exhibit slower disease progression from initial symptom(s) to first functional loss. These patients are characterised by atypical development from 12 to 30 months of age followed by behavioural changes and impairment of fine motor skills typically presenting first. Other symptoms in early- and late-juvenile MLD include a decline in gross motor function, seizures, decreased ability to eat and loss of walking ability.

The impacts of MLD also extend to the wider family, including caregivers and non-affected siblings.

CONCLUSIONS: The presentation of symptoms and impacts of MLD is heterogeneous, resulting in challenges in assessing outcomes, particularly in clinical trial settings. This study helps to clarify the trajectories of MLD phenotypes and can inform further research related to mapping existing clinical outcome assessments (COAs) to the relevant concepts.