Christiane Kehrer1, Saskia Elgün1, Christa Raabe1, Judith Böhringer1, Stefanie Beck-Wödl1, Andrea Bevot1, Nadja Kaiser1, Ludger Schöls1, Ingeborg Krägeloh-Mann1, Samuel Groeschel2. 1. From Department of Paediatric Neurology and Developmental Medicine (C.K., S.E., C.R., J.B., A.B., N.K., I.K.-M., S.G.), University Children's Hospital; Department of Medical Genetics (S.B.-W.), University Hospital Tübingen; Clinical Neurogenetics Section (L.S.), Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) Tübingen (L.S.), Germany Crona Kliniken. 2. From Department of Paediatric Neurology and Developmental Medicine (C.K., S.E., C.R., J.B., A.B., N.K., I.K.-M., S.G.), University Children's Hospital; Department of Medical Genetics (S.B.-W.), University Hospital Tübingen; Clinical Neurogenetics Section (L.S.), Department of Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) Tübingen (L.S.), Germany Crona Kliniken. samuel.groeschel@med.uni-tuebingen.de.
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.
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.
Authors: Margaux C Masten; Camille Corre; Alex R Paciorkowski; Amy Vierhile; Heather R Adams; Jennifer Vermilion; Grace A Zimmerman; Erika F Augustine; Jonathan W Mink Journal: J Inherit Metab Dis Date: 2021-09-07 Impact factor: 4.750
Authors: Shanice Beerepoot; Hans Heijst; Birthe Roos; Mirjam M C Wamelink; Jaap Jan Boelens; Caroline A Lindemans; Peter M van Hasselt; Edwin H Jacobs; Marjo S van der Knaap; Charlotte E Teunissen; Nicole I Wolf Journal: Brain Date: 2022-03-29 Impact factor: 15.255
Authors: Daphne H Schoenmakers; Shanice Beerepoot; Sibren van den Berg; Laura Adang; Annette Bley; Jaap-Jan Boelens; Francesca Fumagalli; Wim G Goettsch; Sabine Grønborg; Samuel Groeschel; Peter M van Hasselt; Carla E M Hollak; Caroline Lindemans; Fanny Mochel; Peter G M Mol; Caroline Sevin; Ayelet Zerem; Ludger Schöls; Nicole I Wolf Journal: Orphanet J Rare Dis Date: 2022-02-14 Impact factor: 4.123
Authors: F Eichler; Caroline Sevin; M Barth; F Pang; K Howie; M Walz; A Wilds; C Calcagni; C Chanson; L Campbell Journal: Orphanet J Rare Dis Date: 2022-10-04 Impact factor: 4.303
Authors: Francesca Fumagalli; Valeria Calbi; Maria Grazia Natali Sora; Maria Sessa; Cristina Baldoli; Paola Maria V Rancoita; Francesca Ciotti; Marina Sarzana; Maddalena Fraschini; Alberto Andrea Zambon; Serena Acquati; Daniela Redaelli; Vanessa Attanasio; Simona Miglietta; Fabiola De Mattia; Federica Barzaghi; Francesca Ferrua; Maddalena Migliavacca; Francesca Tucci; Vera Gallo; Ubaldo Del Carro; Sabrina Canale; Ivana Spiga; Laura Lorioli; Salvatore Recupero; Elena Sophia Fratini; Francesco Morena; Paolo Silvani; Maria Rosa Calvi; Marcella Facchini; Sara Locatelli; Ambra Corti; Stefano Zancan; Gigliola Antonioli; Giada Farinelli; Michela Gabaldo; Jesus Garcia-Segovia; Laetitia C Schwab; Gerald F Downey; Massimo Filippi; Maria Pia Cicalese; Sabata Martino; Clelia Di Serio; Fabio Ciceri; Maria Ester Bernardo; Luigi Naldini; Alessandra Biffi; Alessandro Aiuti Journal: Lancet Date: 2022-01-22 Impact factor: 79.321