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Metachromatic leukodystrophy: A single‐center longitudinal study of 45 patients
Author(s) -
Fumagalli Francesca,
Zambon Alberto A.,
Rancoita Paola M. V.,
Baldoli Cristina,
Canale Sabrina,
Spiga Ivana,
Medaglini Stefania,
Penati Rachele,
Facchini Marcella,
Ciotti Francesca,
Sarzana Marina,
Lorioli Laura,
Cesani Martina,
Natali Sora Maria Grazia,
Del Carro Ubaldo,
Cugnata Federica,
Antonioli Gigliola,
Recupero Salvatore,
Calbi Valeria,
Di Serio Clelia,
Aiuti Alessandro,
Biffi Alessandra,
Sessa Maria
Publication year - 2021
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1002/jimd.12388
Subject(s) - metachromatic leukodystrophy , medicine , juvenile , age of onset , pediatrics , dysphagia , longitudinal study , neurology , disease , surgery , pathology , psychiatry , genetics , biology
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.