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Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers

Authors
  • Harrington, Magdalena1, 2
  • Whalley, Diane3
  • Twiss, James3
  • Rushton, Rebecca3
  • Martin, Susan4
  • Huynh, Lynn5
  • Yang, Hongbo5
  • 1 Shire, a member of the Takeda group of companies, Lexington, MA, USA , Lexington (United States)
  • 2 Present address: Pfizer, 610 Main St, Cambridge, MA, 02139, USA , Cambridge (United States)
  • 3 RTI Health Solutions, Manchester, UK , Manchester (United Kingdom)
  • 4 RTI Health Solutions, Ann Arbor, MI, USA , Ann Arbor (United States)
  • 5 Analysis Group, Inc., Boston, MA, USA , Boston (United States)
Type
Published Article
Journal
Orphanet Journal of Rare Diseases
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Apr 29, 2019
Volume
14
Issue
1
Identifiers
DOI: 10.1186/s13023-019-1060-2
Source
Springer Nature
Keywords
License
Green

Abstract

Background and methodsMetachromatic 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.ResultsThe 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.ConclusionsOur 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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