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000280237 1001_ $$00000-0003-2945-6784$$aBeerepoot, Shanice$$b0
000280237 245__ $$aARSA Variants Associated With Cognitive Decline and Long-Term Preservation of Motor Function in Metachromatic Leukodystrophy.
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000280237 520__ $$aPatients with metachromatic leukodystrophy (MLD) show variable motor and cognitive decline. The ARSA variants c.256C>T, p.(Arg86Trp), c.257G>A, p.(Arg86Gln) and c.542T>G, p.(Ile181Ser) are associated with predominantly cognitive decline. This multinational study analyzed MLD onset type, presenting signs/symptoms, cognitive function, gross motor function, central motor tract involvement, MRI severity score, peripheral neuropathy, and survival of 47 patients (three homozygous for c.256C>T and five, twelve and 27 compound heterozygous for c.256C>T, c.257G>A, or c.542T>G and another ARSA variant, respectively). Eleven underwent hematopoietic stem cell transplantation (HSCT). Onset was late-juvenile (46.8%) or adult (44.7%) with predominantly cognitive decline (n = 40/41 symptomatic patients). At diagnosis, untreated patients typically retained independent walking (100%), sparing of central motor tracts (87.5%), and absence of demyelinating neuropathy (95.5%), which persisted in follow-up for most (76.5%, 71.4%, and 64.7%, respectively). Early-juvenile onset and rapid motor decline occurred only in patients compound heterozygous for c.256C>T and a severe second variant (n = 4), showing central motor tract involvement at diagnosis. One untreated and one treated patient died of disease progression, and another from HSCT complications. All other treated patients retained independent walking, and four of five tested normal cognitive function. Median MRI severity score remained lower in treated (13) than untreated patients (25). The phenotype of c.256C>T carriers depends on the severity of the second ARSA variant. Patients harboring c.257G>A or c.542T>G show late-juvenile or adult onset with cognitive decline and preserved motor function, usually associated with sparing of central motor tracts. In these patients, cognitive function and MRI severity score should be preferred treatment outcomes.
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000280237 650_7 $$2Other$$aARSA gene
000280237 650_7 $$2Other$$aarylsulfatase A
000280237 650_7 $$2Other$$agenetic association studies
000280237 650_7 $$2Other$$ahematopoietic stem cell transplantation
000280237 650_7 $$2Other$$ametachromatic leukodystrophy
000280237 650_7 $$0EC 3.1.6.8$$2NLM Chemicals$$aCerebroside-Sulfatase
000280237 650_2 $$2MeSH$$aHumans
000280237 650_2 $$2MeSH$$aLeukodystrophy, Metachromatic: genetics
000280237 650_2 $$2MeSH$$aMale
000280237 650_2 $$2MeSH$$aFemale
000280237 650_2 $$2MeSH$$aAdult
000280237 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000280237 650_2 $$2MeSH$$aAdolescent
000280237 650_2 $$2MeSH$$aCerebroside-Sulfatase: genetics
000280237 650_2 $$2MeSH$$aYoung Adult
000280237 650_2 $$2MeSH$$aChild
000280237 650_2 $$2MeSH$$aMiddle Aged
000280237 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000280237 650_2 $$2MeSH$$aChild, Preschool
000280237 650_2 $$2MeSH$$aHematopoietic Stem Cell Transplantation
000280237 650_2 $$2MeSH$$aMutation
000280237 7001_ $$00000-0003-1601-7379$$aSchoenmakers, Daphne H$$b1
000280237 7001_ $$00000-0001-7476-4087$$aFumagalli, Francesca$$b2
000280237 7001_ $$00000-0002-2706-7163$$aGroeschel, Samuel$$b3
000280237 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b4
000280237 7001_ $$00000-0003-2437-0252$$aSchiffmann, Raphael$$b5
000280237 7001_ $$aWong, Sheila$$b6
000280237 7001_ $$00000-0003-2389-1232$$aBoespflug-Tanguy, Odile$$b7
000280237 7001_ $$00000-0002-5856-068X$$aSevin, Caroline$$b8
000280237 7001_ $$00000-0003-1466-6957$$aNadjar, Yann$$b9
000280237 7001_ $$00000-0002-5514-0938$$aBley, Annette$$b10
000280237 7001_ $$00000-0003-3970-3486$$aMochel, Fanny$$b11
000280237 7001_ $$00000-0002-3582-1816$$aHorn, Morten A$$b12
000280237 7001_ $$00000-0003-2697-5132$$aBaldoli, Cristina$$b13
000280237 7001_ $$00000-0001-6935-872X$$aLocatelli, Sara$$b14
000280237 7001_ $$0P:(DE-2719)2811940$$aHengel, Holger$$b15
000280237 7001_ $$00000-0003-2506-1961$$aLaugwitz, Lucia$$b16
000280237 7001_ $$00000-0003-0464-1078$$aHollak, Carla E M$$b17
000280237 7001_ $$00000-0001-9410-4617$$aGieselmann, Volkmar$$b18
000280237 7001_ $$00000-0001-8912-0954$$avan der Knaap, Marjo S$$b19
000280237 7001_ $$00000-0003-1721-0728$$aWolf, Nicole I$$b20
000280237 773__ $$0PERI:(DE-600)2006875-X$$a10.1002/jimd.70072$$gVol. 48, no. 5, p. e70072$$n5$$pe70072$$tJournal of inherited metabolic disease$$v48$$x0141-8955$$y2025
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