Natural history of adult-onset metachromatic leukodystrophy

Daniele Mandia¹, Juliette Dufour^{2

3}, Silvia Fenu⁴, Ettore Salsano⁴, Chiara Benzoni⁴, François Sellal^{5

6}, Jeremie Pariente⁷, Nilgün Cengiz⁸, Magali Pettazzoni⁹, Thierry Levade^{10

11}, Foudil Lamari¹², Catherine Caillaud^{13

14}, Roberta La Piana¹⁵, David Brassat^{16

17}, Françoise Durand-Dubief¹⁸, Gérard Besson¹⁹, Sylvie Odent²⁰, David Devos²¹, Mélanie Barbay²², Maria Makrygianni¹, Hojka Gregoric Kumperscak²³, Roseline Froissart⁹, Yann Nadjar²⁴

Affiliations

¹ Neuro-Metabolism Unit, Reference Center for Metabolic and Lysosomal Neurological Diseases, Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France.
² Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France.
³ Paris Brain Institute, Sorbonne Université, Paris, France.
⁴ Unit of Rare Neurological Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.
⁵ Département de Neurologie, Hôpitaux Civils de Colmar, 39, avenue de la Liberté, 68000, Colmar, France.
⁶ INSERM U1329, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
⁷ Neurology, CHU Toulouse, Hôpital Purpan, Toulouse, France.
⁸ Department of Neurology, Faculty of Medicine, Ondokuz MayıS University, Samsun, Turkey.
⁹ Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Bron, France.
¹⁰ Unité Mixte de Recherche INSERM 1037, CNRS 5071, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse (CRCT), Toulouse, France.
¹¹ Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France.
¹² UF Biochimie des Maladies Neuro-Métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
¹³ Metabolic Biochemistry Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
¹⁴ Inserm U1151, CNRS UMR8253, Necker-Enfants Malades Institute, Université de Paris Cité, Paris, France.
¹⁵ Department of Neurology and Neurosurgery, Montreal Neurological Institute, Mcgill University, 3801 rue University, Montreal, QC, H3A 2B4, Canada.
¹⁶ Infinity, Université Toulouse, CNRS, INSERM, UPS, Toulouse, France.
¹⁷ Department of Immunology, CHU Toulouse, Hôpital Purpan, Toulouse, France.
¹⁸ Department of Neurology, Multiple Sclerosis, Myelin Disorders, and Neuro-Inflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon, France.
¹⁹ Neurology Department, Grenoble University Hospital, Grenoble, France.
²⁰ Service de Génétique Clinique, Centre de Référence "Anomalies du Développement et Syndromes Malformatifs" de l'Inter-Région Ouest, CHU Rennes, Univ Rennes, CNRS, INSERM, IGDR (Institut de Génétique Et Développement de Rennes) - UMR 6290, ERL U1305, Rennes, France.
²¹ Medical Pharmacology Department University of Lille & Parkinson's Disease Centre of Excellence, CHU Lille, INSERM U1172 - Degenerative & Vascular Cognitive Disorders, LilNCog, Lille Neuroscience & Cognition, LICEND, NS-Park Network, Lille, France.
²² Service de Neurologie CHU Amiens et Laboratoire de Neurosciences Fonctionnelles et Pathologies, Université de Picardie Jules Verne, Amiens, France.
²³ Department for Child and Adolescent Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
²⁴ Neuro-Metabolism Unit, Reference Center for Metabolic and Lysosomal Neurological Diseases, Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France. yann.nadjar@aphp.fr.

PMID: 40167764
PMCID: PMC11961487
DOI: 10.1007/s00415-025-12997-2

Natural history of adult-onset metachromatic leukodystrophy

Daniele Mandia et al. J Neurol. 2025.

. 2025 Apr 1;272(4):303.

doi: 10.1007/s00415-025-12997-2.

Authors

Affiliations

¹ Neuro-Metabolism Unit, Reference Center for Metabolic and Lysosomal Neurological Diseases, Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France.
² Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France.
³ Paris Brain Institute, Sorbonne Université, Paris, France.
⁴ Unit of Rare Neurological Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.
⁵ Département de Neurologie, Hôpitaux Civils de Colmar, 39, avenue de la Liberté, 68000, Colmar, France.
⁶ INSERM U1329, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
⁷ Neurology, CHU Toulouse, Hôpital Purpan, Toulouse, France.
⁸ Department of Neurology, Faculty of Medicine, Ondokuz MayıS University, Samsun, Turkey.
⁹ Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Bron, France.
¹⁰ Unité Mixte de Recherche INSERM 1037, CNRS 5071, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse (CRCT), Toulouse, France.
¹¹ Laboratoire de Biochimie, Institut Fédératif de Biologie, CHU Purpan, Toulouse, France.
¹² UF Biochimie des Maladies Neuro-Métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
¹³ Metabolic Biochemistry Department, Necker-Enfants Malades Hospital, AP-HP, Université de Paris Cité, Paris, France.
¹⁴ Inserm U1151, CNRS UMR8253, Necker-Enfants Malades Institute, Université de Paris Cité, Paris, France.
¹⁵ Department of Neurology and Neurosurgery, Montreal Neurological Institute, Mcgill University, 3801 rue University, Montreal, QC, H3A 2B4, Canada.
¹⁶ Infinity, Université Toulouse, CNRS, INSERM, UPS, Toulouse, France.
¹⁷ Department of Immunology, CHU Toulouse, Hôpital Purpan, Toulouse, France.
¹⁸ Department of Neurology, Multiple Sclerosis, Myelin Disorders, and Neuro-Inflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Lyon, France.
¹⁹ Neurology Department, Grenoble University Hospital, Grenoble, France.
²⁰ Service de Génétique Clinique, Centre de Référence "Anomalies du Développement et Syndromes Malformatifs" de l'Inter-Région Ouest, CHU Rennes, Univ Rennes, CNRS, INSERM, IGDR (Institut de Génétique Et Développement de Rennes) - UMR 6290, ERL U1305, Rennes, France.
²¹ Medical Pharmacology Department University of Lille & Parkinson's Disease Centre of Excellence, CHU Lille, INSERM U1172 - Degenerative & Vascular Cognitive Disorders, LilNCog, Lille Neuroscience & Cognition, LICEND, NS-Park Network, Lille, France.
²² Service de Neurologie CHU Amiens et Laboratoire de Neurosciences Fonctionnelles et Pathologies, Université de Picardie Jules Verne, Amiens, France.
²³ Department for Child and Adolescent Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
²⁴ Neuro-Metabolism Unit, Reference Center for Metabolic and Lysosomal Neurological Diseases, Neurology Department, Hôpital Pitié-Salpêtrière, Paris, France. yann.nadjar@aphp.fr.

PMID: 40167764
PMCID: PMC11961487
DOI: 10.1007/s00415-025-12997-2

No abstract available

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflict of interest regarding this work. Ethical approval: This study has been approved by the ethics committee and it have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The manuscript does not contain clinical studies or patient data.

Figures

**Fig. 1**
Global cohort of patients (survey + literature), distributed based on the first symptom at onset (n = 62)

**Fig. 2**
Cumulative probability (Kaplan–Meier analysis) of patients being preserved of severe disability (loss of speech, loss of independent walking, wheelchair bound, gastrostomy, and death) in recruited patients having adult-onset MLD (n = 62)

See this image and copyright information in PMC

References

1. Gieselmann V, Krägeloh-Mann I (2010) Metachromatic leukodystrophy—an update. Neuropediatrics 41(01):1–6. 10.1055/s-0030-1253412 - DOI - PubMed
1. Takahashi T, Suzuki T (2012) Role of sulfatide in normal and pathological cells and tissues. J Lipid Res 53(8):1437–1450. 10.1194/jlr.R026682 - DOI - PMC - PubMed
1. Kehrer C et al (2021) Association of age at onset and first symptoms with disease progression in patients with metachromatic leukodystrophy. Neurology 96(2):e255–e266. 10.1212/WNL.0000000000011047 - DOI - PubMed
1. Fumagalli F et al (2022) Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. The Lancet 399(10322):372–383. 10.1016/S0140-6736(21)02017-1 - DOI - PMC - PubMed
1. van Rappard DF et al (2016) Efficacy of hematopoietic cell transplantation in metachromatic leukodystrophy: the Dutch experience. Blood 127(24):3098–3101. 10.1182/blood-2016-03-708479 - DOI - PubMed

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Natural history of adult-onset metachromatic leukodystrophy

Affiliations

Natural history of adult-onset metachromatic leukodystrophy

Authors

Affiliations

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources