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Abstract
Objective To compare disease progression between different onset forms of metachromatic leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression.
Methods Clinical, genetic, and biochemical parameters were analyzed within a nationwide study of patients with late-infantile (LI; onset age ≤2.5 years), early-juvenile (EJ; onset age 2.6 to <6 years), late-juvenile (LJ; onset age 6 to <16 years), and adult (onset age ≥16 years) forms of MLD. First symptoms were categorized as motor symptoms only, cognitive symptoms only, or both. Standardized clinical endpoints included loss of motor and language functions, as well as dysphagia/tube feeding.
Results Ninety-seven patients with MLD were enrolled. Patients with LI (n = 35) and EJ (n = 18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n = 38) and adult-onset (n = 6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independently of their age at onset. A certain genotype-phenotype correlation was observed.
Conclusions In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counseling and therapy.
Classification of Evidence This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.
Glossary
- ARSA=
- arylsulfatase A;
- EJ=
- early-juvenile;
- GMFC=
- Gross Motor Function Classification;
- LI=
- late-infantile;
- LJ=
- late-juvenile;
- MLD=
- metachromatic leukodystrophy
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Class of Evidence: NPub.org/coe
- Received February 5, 2020.
- Accepted in final form August 27, 2020.
- © 2020 American Academy of Neurology
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- Author Response: Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy
- Reader Response: Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy
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