Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
04
05
2023
received:
10
03
2023
accepted:
10
05
2023
medline:
19
7
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
Metachromatic leukodystrophy is a lysosomal storage disease caused by deficient arylsulfatase A. It is characterized by progressive demyelination and thus mainly affects the white matter. Hematopoietic stem cell transplantation may stabilize and improve white matter damage, yet some patients deteriorate despite successfully treated leukodystrophy. We hypothesized that post-treatment decline in metachromatic leukodystrophy might be caused by gray matter pathology. Three metachromatic leukodystrophy patients treated with hematopoietic stem cell transplantation with a progressive clinical course despite stable white matter pathology were clinically and radiologically analyzed. Longitudinal volumetric MRI was used to quantify atrophy. We also examined histopathology in three other patients deceased after treatment and compared them with six untreated patients. The three clinically progressive patients developed cognitive and motor deterioration after transplantation, despite stable mild white matter abnormalities on MRI. Volumetric MRI identified cerebral and thalamus atrophy in these patients, and cerebellar atrophy in two. Histopathology showed that in brain tissue of transplanted patients, arylsulfatase A expressing macrophages were clearly present in the white matter, but absent in the cortex. Arylsulfatase A expression within patient thalamic neurons was lower than in controls, the same was found in transplanted patients. Neurological deterioration may occur after hematopoietic stem cell transplantation in metachromatic leukodystrophy despite successfully treated leukodystrophy. MRI shows gray matter atrophy, and histological data demonstrate absence of donor cells in gray matter structures. These findings point to a clinically relevant gray matter component of metachromatic leukodystrophy, which does not seem sufficiently affected by transplantation.
Identifiants
pubmed: 37212343
doi: 10.1002/acn3.51796
pmc: PMC10351661
doi:
Substances chimiques
Cerebroside-Sulfatase
EC 3.1.6.8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1146-1159Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS115052
Pays : United States
Informations de copyright
© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Hum Mol Genet. 2019 Jun 1;28(11):1810-1821
pubmed: 30657900
JAMA Neurol. 2016 Sep 1;73(9):1133-40
pubmed: 27400410
Eur Neurol. 1980;19(5):294-307
pubmed: 6249606
N Engl J Med. 2018 May 17;378(20):1898-1907
pubmed: 29688815
Science. 2013 Aug 23;341(6148):1233158
pubmed: 23845948
Best Pract Res Clin Endocrinol Metab. 2015 Mar;29(2):261-73
pubmed: 25987178
Bone Marrow Transplant. 2013 Mar;48(3):369-75
pubmed: 22941383
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Blood. 2016 Jun 16;127(24):3098-101
pubmed: 27118454
Mult Scler. 2017 Mar;23(3):420-431
pubmed: 27246142
Ann N Y Acad Sci. 2015 Sep;1351:99-113
pubmed: 26200258
Ann Clin Transl Neurol. 2020 Feb;7(2):169-180
pubmed: 31967741
AJNR Am J Neuroradiol. 2009 Nov;30(10):1893-7
pubmed: 19797797
Neurology. 2012 Oct 16;79(16):1662-70
pubmed: 22993277
Lancet. 2022 Jan 22;399(10322):372-383
pubmed: 35065785
Brain. 2011 Nov;134(Pt 11):3333-41
pubmed: 22006980
J Inherit Metab Dis. 2011 Oct;34(5):1095-102
pubmed: 21698385
Mult Scler. 2018 Jul;24(8):1055-1066
pubmed: 28617152
Acta Paediatr (Stockh). 1960 Mar;49:135-53
pubmed: 14398772
Acta Neuropathol. 2001 Mar;101(3):249-55
pubmed: 11307625
Neurology. 2001 Oct 23;57(8):1411-6
pubmed: 11673581
Ann Clin Transl Neurol. 2015 Sep;2(9):932-40
pubmed: 26401514
Mol Genet Metab. 2020 Sep - Oct;131(1-2):235-244
pubmed: 32792226
AJNR Am J Neuroradiol. 2012 Oct;33(9):1731-9
pubmed: 22538069
JAMA Neurol. 2013 Jun;70(6):779-82
pubmed: 23608771
Hum Mol Genet. 2021 Feb 4;29(23):3807-3817
pubmed: 33367737
Lancet. 2016 Jul 30;388(10043):476-87
pubmed: 27289174
Neurology. 2016 Aug 23;87(8):752-8
pubmed: 27440150
Hum Mol Genet. 2011 Apr 15;20(R1):R42-53
pubmed: 21459776