Late juvenile metachromatic leukodystrophy treated with bone marrow transplantation

Navarro, Cristina; Fernández, José Marı́a; Domı́nguez, Carmen; Fachal, C.; Álvarez, Manuel Díaz

doi:10.1212/wnl.46.1.254

Cited by 28 publications

(12 citation statements)

References 2 publications

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“…6,7,13,21 Also, the fact that HSCT is not standardized at different centers prevents us from finding a definitive answer to the question of whether HSCT is a safe and effective treatment for adult and lateonset juvenile MLD. For example, regionalization and specialization has been shown to reduce TRM as well as acute and chronic GVHD.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…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. [6][7][8][9][10][11][12][13] …”

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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“…7,12,13 In slowly progressing late juvenile cases with only minor symptoms, a stable clinical, neurophysiological and neuropsychological state has been reported after BMT. 4,14 However, deterioration may continue for up to 2 years after BMT and mental function stabilizes at a lower level than the baseline IQ. 7 Only a few BMTs for adult MLD have been performed.…”

Section: Discussionmentioning

confidence: 99%

“…In reports of infantile and juvenile cases treated with BMT, nerve conduction has remained unchanged. 14,[16][17][18] The method used to assess peripheral nerve conduction in this study (ENeG-Ix) may be more sensitive for detecting changes over time.…”

Section: Discussionmentioning

confidence: 99%

Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy

Solders¹,

Celsing²,

Hagenfeldt³

et al. 1998

Bone Marrow Transplant

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Summary:A 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy and was followed for 4 years after bone marrow transplantation (BMT). MRI, neurophysiological tests (EEG, ENeG, VEP, SEP and BAEP) and neuropsychological assessment were performed before, and repeatedly after BMT. MRI showed symmetrical white matter lesions in the frontal and parieto-occipital lobes and in the corpus callosum. EEG showed frontal and temporal slow wave abnormalities and nerve conduction was slow. Neuropsychological tests showed cognitive impairment in executive functions, decline in visuospatial-constructive and spatial memory tasks and disorganized thinking. IQ was low (52), with slightly better values for verbal IQ than for performance IQ. After BMT, the patient was followed for 4 years. Clear improvements were seen in EEG, in peripheral nerve conduction and in neuropsychological tests (especially in verbal IQ). MRI findings were unchanged. We believe that the improvement in our patient resulted from the bone marrow transplantation. Keywords: metachromatic leukodystrophy; bone marrow transplantationIn metachromatic leukodystrophy (MLD), the accumulation of galactosyl sulphatide in lysosomes, due to an inherited deficiency of arylsulphatase A, causes demyelination in the central and peripheral nervous systems. Clinical symptoms vary. Depending on the age at onset of clinical symptoms and on the course of the disease, MLD is classified as late infantile (6 months to 2 years), early juvenile (4 to 6 years), late juvenile (6 to 16 years) and adult (Ͼ16 years) types. In adult MLD, psychiatric symptoms dominate with a change in personality, poor school or job performance and emotional lability. Disorganized thinking and impairment of memory functions then occur and hypomania/depression Correspondence: Dr G Solders, Department of Neurology, Huddinge Hospital, S-141 86 Sweden Received 27 April 1998; accepted 15 July 1998 or psychosis is common. 1 Adult MLD may develop as a schizophrenic disorder 2 or it may present as polyneuropathy. 3 Bone marrow transplantation (BMT) is recommended for presymptomatic cases in infants and children with a sibling with MLD and for early cases of juvenile MLD. BMT has been performed in only a few cases of adult MLD. 4 Case report and methodsA 28-year-old woman with a 4 year history of slowly progressing 'frontal dementia' was diagnosed as having adult metachromatic leukodystrophy. She had previously been healthy, except for slight hypothyroidism, for which she had been treated. She had completed 12 years of school with excellent grades and had started university studies. At 24 years old, she gave birth to twins. After that, her parents noted a slow change in personality, with increasing difficulties in daily living and in caring for her children. Dyscalculia and inertia were observed. She appeared depressed for a while and then developed a schizophreniform state and was referred to a psychiatric clinic. She became progressi...

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“…The reported course, following HSCT, in juvenile/ adult forms appears to be often comparable with the natural course of the expected disease, which is usually characterized by a slow progression of symptoms. [30][31][32][33][34][35] Despite full engraftment and normalcy of enzymatic activity, in these forms the only benefit might be an improved survival in selected cases, whereas failure to obtain an improved or stabilized quality of life appears common. 27,28,36 Recent clinical evidence obtained in patients affected by globoid cell leukodystrophy, an LSD related to MLD and consequent to the deficiency of the enzyme involved in the downstream reaction, following ARSA, in the catabolism of myelin lipids, indicate that cord blood transplantation may favorably alter the natural history of infantile forms by delaying onset and progression if performed in asymptomatic newborns at less than 4 weeks of age.…”

Section: Hematopoietic Cell Transplantationmentioning

confidence: 99%