4.4 Article

Metachromatic leukodystrophy: A single-center longitudinal study of 45 patients

期刊

JOURNAL OF INHERITED METABOLIC DISEASE
卷 44, 期 5, 页码 1151-1164

出版社

WILEY
DOI: 10.1002/jimd.12388

关键词

longitudinal study; metachromatic leukodystrophy; MLD; natural history

资金

  1. GlaxoSmithKline (GSK)
  2. Orchard Therapeutics
  3. Fondazione Telethon

向作者/读者索取更多资源

This study characterizes the natural course of metachromatic leukodystrophy (MLD) and explores differences between different subgroups. It identifies factors influencing disease progression and highlights differences in disease-related milestones among MLD subtypes. The study also provides insights into reliable clinical and instrumental tools for monitoring disease progression and evaluating therapeutic interventions.
In this study, we characterize the natural course of metachromatic leukodystrophy (MLD), explore intra/inter group differences, and identify biomarkers to monitor disease progression. This is a longitudinal observational study. Genotype and characteristics at disease onset were recorded. Time-to-event analyses were performed to assess time to major disease-related milestones in different subgroups. Longitudinal trajectories of nerve conduction velocities (NCV), brain MRI score, and brainstem auditory evoked responses (BAERs) were described. We recruited 22 late-infantile, 14 early-juvenile, 5 late-juvenile, and 4 adult MLD patients. Thirty-four were prospectively evaluated (median FU time 43 months). In late-infantile patients, the attainment of independent walking was associated with a later age at dysphagia. In early-juvenile, the presence of isolated cognitive impairment at onset was not a favorable prognostic factor. Late-infantile and early-juvenile subjects showed similar rapid loss of ambulation and onset of seizures, but late-infantile displayed earlier loss of trunk control, dysphagia, and death. We found significant differences in all major disease-related milestones (except death) between early-juvenile and late-juvenile patients. Late-juvenile and adult patients both presented with a predominant cognitive impairment, mild/no peripheral neuropathy, lower brain MRI score at plateau compared to LI/EJ, and later cerebellar involvement. NCV and BAER were consistently severely abnormal in late-infantile but not in older subjects, in whom both NCV and BAER were variably affected, with no deterioration over time in some cases. This study clarifies intra/inter group differences between MLD subtypes and provides additional indications regarding reliable clinical and instrumental tools to monitor disease progression and to serve as areference to evaluate the efficacy of future therapeutic interventions inthe different MLD variants.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据