Clinical Symptoms of Adult Metachromatic Leukodystrophy and Arylsulfatase A Pseudodeficiency

Hageman, Alexia; Gabreëls, F.J.M.; Jong, J.G.N. de; Gabreëls-Festen, A.A.W.M.; Berg, C. J. M. G. van den; Oost, B.A. van; Wevers, Ron A.

doi:10.1001/archneur.1995.00540280098023

Cited by 51 publications

(42 citation statements)

References 23 publications

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“…In their group of 13 patients with confirmed adult MLD, the most common symptoms were ataxia and behavioural abnormalities with only 1 patient suffering from psychosis. The findings were similar in the group of 24 patients with confirmed MLD described in the literature, among whom only 4 were psychotic (Hageman et al, 1995).…”

Section: Discussionsupporting

confidence: 85%

“…The disease is caused by a deficiency of the enzyme arylsulfatase A, which hydrolyzes various sulfatides, including the major sulfate-containing lipids of the nervous system. Sulfatide accumulation can be found in the brain and peripheral nerves and nonneural organs (kidney and gallbladder) (Hageman et al, 1995). The incidence of MLD is estimated between 1 and 5 cases per 100 000 newborns (Rentrop et al, 1999) There are 3 types of MLD: late infantile, juvenile and adult.…”

Section: Discussionmentioning

confidence: 99%

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Childhood and Adolescent Schizophrenia and Other Early-Onset Psychoses

Kumperščak¹

2011

Psychiatric Disorders - Trends and Developments

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Childhood and Adolescent Schizophrenia and Other Early-Onset Psychoses

Kumperščak¹

2011

Psychiatric Disorders - Trends and Developments

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“…3 The disease has a variable, often slow but progressive course with a mean survival of 12 years after onset of the initial symptoms. 4 After treatment with allogeneic hematopoietic SCT (HSCT), transplanted macrophages migrate through the blood-brain barrier and then differentiate into microglia, which replace ARSA-deficient microglia 5 and also support them with functional ARSA through cross-correction of the enzyme. 1 HSCT is currently the only treatment in clinical use for late-juvenile and adult MLD, but the long-term results that have been published are few and inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Solders

Martin

Andersson

et al. 2014

Bone Marrow Transplant

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In metachromatic leukodystrophy (MLD), the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) leads to demyelination in the central and peripheral nervous system and ultimately to death. Allogeneic hematopoietic SCT (HSCT) is currently the only treatment for adult and late-onset juvenile MLD, although it is still in question because of insufficient follow-up. We wanted to determine whether HSCT could halt the progression of adult and late-onset juvenile MLD. Four treated unrelated patients and three untreated siblings were included in the study, and followed regularly for up to 18 years after transplantation. The patients were assessed from clinical examination, ARSA enzyme levels, magnetic resonance imaging of the brain and neuropsychological and neurophysiological tests. In the treated patients, ARSA levels were normal up to 18 years after transplantation. The parameters evaluated stabilized and remained stable after a latency period of 12-24 months. Two patients live normal lives, partially in a protected environment. The other two patients stabilized at a low cognitive and functional level. One of the controls is demented, one is in a vegetative state and one died. We conclude that, in comparison with their untreated siblings, HSCT halted the progression of the disease in our treated patients.

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“…1,2 The course is slowly progressive, variable and has a mean survival of 12 years after disease onset. 3 SCT has been used to treat several lysosomal storage diseases. 4 After SCT, donor-derived cells can migrate into the central nervous system and can mediate the crosscorrection of ARSA in neighboring neuronal and glial cells.…”

Section: Introductionmentioning

confidence: 99%

Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature

Hosson

Warrenburg

Preijers

et al. 2010

Bone Marrow Transplant

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Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.

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Clinical Symptoms of Adult Metachromatic Leukodystrophy and Arylsulfatase A Pseudodeficiency

Cited by 51 publications

References 23 publications

Childhood and Adolescent Schizophrenia and Other Early-Onset Psychoses

Childhood and Adolescent Schizophrenia and Other Early-Onset Psychoses

Hematopoietic SCT: a useful treatment for late metachromatic leukodystrophy

Adult metachromatic leukodystrophy treated by allo-SCT and a review of the literature

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