Harrington M, Whalley D, Twiss J, Rushton R, Martin S, Huynh L, Yang H. Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers. Orphanet J Rare Dis. 2019 Apr 29;14(1):89. doi: 10.1186/s13023-019-1060-2

BACKGROUND AND METHODS: Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease caused by deficient activity of arylsulfatase A. Neurological involvement results in severe disability and premature death, but understanding of the natural history of the disease remains limited. In this study, 32 caregivers of patients with MLD in the USA (16 with late-infantile MLD; 16 with juvenile MLD) were interviewed about their experiences of the disease. Qualitative analysis of the interview transcripts was performed to gain insights into symptom onset, the diagnostic process and disease progression, with a focus on the differences between late-infantile and juvenile MLD.

RESULTS: The mean ages of patients at interview were 7.6 years and 20.7 years for individuals with late-infantile and juvenile MLD, respectively. Patients with late-infantile MLD had a mean age of 1.5 years at symptom onset and 2.6 years at diagnosis. The most common initial symptoms in this group related to problems with gross motor function (12/16 patients); 11 patients never learned to walk independently. For patients with juvenile MLD, the mean ages at symptom onset and diagnosis were 8.7 years and 11.6 years, respectively. Cognitive or social/behavioural problems were the most common first reported symptoms in this group (9/16 and 7/16 patients, respectively); these were generally followed by deterioration in motor function. The rate of functional decline was more rapid in patients with late-infantile MLD than those with juvenile MLD; the mean time from first symptom to first functional loss was 1 year versus 6.1 years, respectively. Nine patients with juvenile MLD and three with late-infantile MLD had undergone a haematopoietic stem cell transplant; outcomes following transplant were variable.

CONCLUSIONS: Our data highlight clear overall differences in symptom profiles and disease progression between late-infantile and juvenile MLD, but also indicate some degree of interindividual variability within each subtype. These findings are broadly consistent with previously published descriptions of MLD and enhance our knowledge of the natural history of the disease, which ultimately should help to improve patient care and aid assessments of the effectiveness of disease-related interventions in the future.

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