Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Adang Laura Ann, Groeschel Samuel, Grzyb Chloe, D'Aiello Russell, Gavazzi Francesco, Sherbini Omar, Bronner Nowa, Patel Akshilkumar, Vincent Ariel, Sevagamoorthy Anjana, Mutua Sylvia, Muirhead Kayla, Schmidt Johanna, Pizzino Amy, Yu Emily, Jin Danielle, Eichler Florian, Fraser Jamie L, Emrick Lisa, Van Haren Keith, Boulanger Jean-Martin, Ruzhnikov Maura, Sylvain Michel, Nguyen Cam-Tu Émilie, Potic Ana, Keller Stephanie, Fatemi Ali, Uebergang Eloise, Poe Michele, Yazdani Pouneh Amir, Bernat John, Lindstrom Kristen, Bonkowsky Joshua L, Bernard Genevieve, Stutterd Chloe A, Orchard Paul, Gupta Ashish O, Ljungberg Merete, Groenborg Sabine, Zambon Alberto, Locatelli Sara, Fumagalli Francesca, Elguen Saskia, Kehrer Christiane, Krägeloh-Mann Ingeborg, Shults Justine, Vanderver Adeline, Escolar Maria L
Аннотация
METHODS: The specific ages of gain and loss of developmental milestones were captured from the medical records of individuals affected by MLD. Milestone acquisition was characterized as: on target (obtained before the age limit of 90th percentile plus 2 standard deviations compared to a normative dataset), delayed (obtained after 90th percentile plus 2 standard deviations), or plateau (skills never gained). Regression was defined as the age at which skills were lost. LI-MLD was defined by age at onset before 2.5 years.
RESULTS: Across an international cohort, 351 subjects were included (n = 194 LI-MLD subcohort). The median age at presentation of the LI-MLD cohort was 1.4 years (25th-75th %ile: 1.0-1.5). Within the LI-MLD cohort, 75/194 (39%) had developmental delay (or plateau) prior to MLD clinical presentation. Among the LI-MLD cohort with a minimum of 1.5 years of follow-up (n = 187), 73 (39.0%) subjects never attained independent ambulation. Within LI-MLD + delay subcohort, the median time between first missed milestone target to MLD decline was 0.60 years (maximum distance from delay to onset: 1.9 years).
INTERPRETATION: Early developmental delay precedes regression in a subset of children affected by LI-MLD, defining the onset of neurologic dysfunction earlier than previously appreciated. The use of realworld data prior to diagnosis revealed an early deviation from typical development. Close monitoring for early developmental delay in presymptomatic individuals may help in earlier diagnosis with important consequences for treatment decisions.