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Genomes and Genes | metachromatic leukodystrophySummarySummary: An autosomal recessive lysosomal storage disease caused by a deficiency of CEREBROSIDE-SULFATASE leading to an accumulation of cerebroside sulfate in the nervous system and other organs. Pathologic features include diffuse demyelination and metachromatically-staining granules within glial cells, macrophages, and free in tissue. Clinical subtypes include late infantile, juvenile, and adult forms. The late infantile form presents at 12-18 months of age with progressive psychomotor retardation, ATAXIA, spasticity, and OPTIC ATROPHY. The juvenile form has onset at 4-12 years and features behavioral alterations and ataxia followed by spasticity, DEMENTIA, and visual loss. The adult form presents in the second decade or later with psychiatric manifestations, gait difficulties, and less often as a peripheral neuropathy. (From Menkes, Textbook of Child Neurology, 5th ed, pp192-5) Top Publications
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Late-onset metachromatic leukodystrophy: genotype strongly influences phenotypeH Rauschka
Center for Brain Research, Medical University of Vienna, Department of Neurology, Hospital Lainz, Austria
Neurology 67:859-63. 2006BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity...
Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlationA Biffi
San Raffaele Telethon Institute for Gene Therapy Paediatric Clinical Research Unit, San Raffaele Scientiffic Institute, Milan, Italy
Clin Genet 74:349-57. 2008b>Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder resulting from the inherited deficiency of the arylsulfatase A (ARSA) enzyme. Currently, no valid therapeutic options are available for affected patients...- In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected miceA Consiglio
Telethon Institute for Gene Therapy and Department of Neurology, Scientific Institute H.S. Raffaele HSR-TIGET, Milan, Italy
Nat Med 7:310-6. 2001b>Metachromatic leukodystrophy (MLD) is a lipidosis caused by deficiency of arylsulfatase A (ARSA). Although the genetics of MLD are known, its pathophysiology is not understood... - Metachromatic leukodystrophy: genetics, pathogenesis and therapeutic optionsVolkmar Gieselmann
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhems Universität Bonn, Bonn, Germany
Acta Paediatr Suppl 97:15-21. 2008b>Metachromatic leukodystrophy is a lysosomal storage disease caused by the deficiency of arylsulphatase A (ASA). This leads to storage of the membrane lipid sulphatide, which is abundant in myelin... - Expression and purification of a human, soluble Arylsulfatase A for Metachromatic Leukodystrophy enzyme replacement therapySabata Martino
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, University of Perugia, Via del Giochetto, Italy
J Biotechnol 117:243-51. 2005..production of active Arylsulfatase A is a key step in the development of enzyme replacement therapy for Metachromatic Leukodystrophy. To obtain large amounts of purified Arylsulfatase A for therapeutic use, we combined a retroviral .. - Metachromatic leukodystrophy in the Navajo Indian population: a splice site mutation in intron 4 of the arylsulfatase A geneN M Pastor-Soler
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
Hum Mutat 4:199-207. 1994b>Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder of myelin metabolism, resulting from the inability to properly degrade 3-sulfogalactosylceramide (sulfatide)... - Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severityStefano Regis
Laboratorio di Diagnosi Pre e Postnatale di Malattie Metaboliche, Istituto G Gaslini, Largo G Gaslini 5, 16147 Genova, Italy
Hum Genet 110:351-5. 2002..We identified a late infantile metachromatic leukodystrophy patient carrying on one allele the new E253K mutation and the known T391S polymorphism, and on the .. - Metachromatic leukodystrophy: molecular genetics and an animal modelV Gieselmann
Biochemisches Institut der Christian Albrechts Universität zu Kiel, Germany
J Inherit Metab Dis 21:564-74. 1998b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA; EC 3.1.6.8). Deficiency of this enzyme causes intralysosomal storage of the sphingolipid cerebroside sulphate... - Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndromeW Krivit
University of Minnesota and Institute of Human Genetics, Minneapolis 55455, USA
Curr Opin Hematol 6:377-82. 1999..Treatment is directed to prevent or ameliorate the inexorable neurological deterioration that is the major pathophysiological event in all of these inherited metabolic storage diseases... - AAV1 mediated co-expression of formylglycine-generating enzyme and arylsulfatase a efficiently corrects sulfatide storage in a mouse model of metachromatic leukodystrophyToshiyuki Kurai
Department of Biochemistry and Molecular Biology, Nippon Medical School, Bunkyo ku, Tokyo, Japan
Mol Ther 15:38-43. 2007b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA) and is characterized by deposition of sulfatide in all organs, particularly the nervous system... - Diagnosis of metachromatic leukodystrophy by immune quantification of arylsulphatase A protein and activity in dried blood spotsMohd A F Tan
Clin Chem 54:1925-7. 2008 - Missense mutations as a cause of metachromatic leukodystrophy. Degradation of arylsulfatase A in the endoplasmic reticulumPeter Poeppel
, , Germany
FEBS J 272:1179-88. 2005b>Metachromatic leukodystrophy is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA)... 
Multiple mutations are responsible for the high frequency of metachromatic leukodystrophy in a small geographic areaU Heinisch
Institut für Biochemie II, Universitat Gottingen, Germany
Am J Hum Genet 56:51-7. 1995b>Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. The disease occurs panethnically, with an estimated frequency of 1/40,000...- Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophyUlrich Matzner
Institut Für Physiologische Chemi, Rheinische Friedrich Wilhelms Universitat, Nussallee 11, 53115 Bonn, Germany
Hum Mol Genet 14:1139-52. 2005A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy, which is characterized by accumulation of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide)... - Two new arylsulfatase A (ARSA) mutations in a juvenile metachromatic leukodystrophy (MLD) patientA L Fluharty
Mental Retardation Research Center, University of California School of Medicine, Los Angeles
Am J Hum Genet 49:1340-50. 1991Fragments of the arylsulfatase A (ARSA) gene from a patient with juvenile-onset metachromatic leukodystrophy (MLD) were amplified by PCR and ligated into MP13 cloning vectors... - Molecular bases of metachromatic leukodystrophy in Polish patientsAgnieszka Lugowska
Department of Genetics, Institute of Psychiatry and Neurology, Al Sobieskiego 9, Warsaw, Poland
J Hum Genet 55:394-6. 2010Our preliminary studies on 43 unrelated Polish patients suffering from different types of metachromatic leukodystrophy (MLD) showed that four mutations in the ARSA gene accounted for 55% of mutated alleles (c.459+1G>A, p.P426L, p... - Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiencyX L Zhang
Department of Medicine, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Philadelphia, PA 19107
Proc Natl Acad Sci U S A 87:1426-30. 1990..While most patients with metachromatic leukodystrophy have mutations in the gene for arylsulfatase A, some patients have deficient SAP-1, as determined by .. - Sulfatide storage in neurons causes hyperexcitability and axonal degeneration in a mouse model of metachromatic leukodystrophyMatthias Eckhardt
Institute of Physiological Chemistry, University of Bonn, 53115 Bonn, Germany
J Neurosci 27:9009-21. 2007b>Metachromatic leukodystrophy is a lysosomal storage disorder caused by deficiency in the sulfolipid degrading enzyme arylsulfatase A (ASA)... - A non-glycosylated and functionally deficient mutant (N215H) of the sphingolipid activator protein B (SAP-B) in a novel case of metachromatic leukodystrophy (MLD)D Wrobe
Kekule Institut fur Organische Chemie und Biochemie, Universitat Bonn, Germany
J Inherit Metab Dis 23:63-76. 2000..the lysosomal accumulation of sulphatides and other sphingolipids, resulting in variant forms of metachromatic leukodystrophy (MLD)... - Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A-deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophyHariharasubramanian Ramakrishnan
Institute of Physiological Chemistry, Rheinische Friedrich Wilhelms University of Bonn, 53115 Bonn, Germany
J Neurosci 27:9482-90. 2007b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ASA)... - Embryonic stem cell-based reduction of central nervous system sulfatide storage in an animal model of metachromatic leukodystrophyD Klein
Institute of Physiological Chemistry, University of Bonn, Bonn, Germany
Gene Ther 13:1686-95. 2006..overexpress human arylsulfatase A (hASA) can cross-correct the metabolic defect in an animal model of metachromatic leukodystrophy (MLD). Transfected ES cells showed an up to 30-fold increase in ASA activity... - Multiple cranial nerve enhancement: a new MR imaging finding in metachromatic leukodystrophyAntonio C M Maia
AJNR Am J Neuroradiol 28:999. 2007 - Prosaposin deficiency and saposin B deficiency (activator-deficient metachromatic leukodystrophy): report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutationsLadislav Kuchar
Charles University in Prague, 1st Medical Faculty, Institute of Inherited Metabolic Disorders of 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic
Am J Med Genet A 149:613-21. 2009..a severe neurovisceral dystrophy and died as a neonate, and the other with SapB-d, who presented with a metachromatic leukodystrophy-like disorder but had normal arylsulfatase activity... - Enzyme replacement improves ataxic gait and central nervous system histopathology in a mouse model of metachromatic leukodystrophyUlrich Matzner
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Bonn, Germany
Mol Ther 17:600-6. 2009..To assess the efficacy of long-term ERT in metachromatic leukodystrophy (MLD), an LSD with prevailing nervous system disease, we treated immunotolerant arylsulfatase A (ASA) .. - Multipotential neural precursors transplanted into the metachromatic leukodystrophy brain fail to generate oligodendrocytes but contribute to limit brain dysfunctionM I Givogri
Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
Dev Neurosci 30:340-57. 2008..the effects of high levels of potentially toxic substances such as sulfatides--which accumulate in metachromatic leukodystrophy (MLD)--on this regenerative ability are still largely unclear... - Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophyUlrich Matzner
Institut für Physiologische Chemie and LIMES, Membrane Biology and Lipid Biochemistry Unit, c o Kekulé Institut für Organische Chemie und Biochemie, Rheinische Friedrich Wilhelms University, 53115 Bonn, Germany
J Biol Chem 284:9372-81. 2009..progressive intralysosomal accumulation of sulfatide, and the fatal lysosomal storage disease metachromatic leukodystrophy. We studied the coupled Sap B-ASA reaction in vitro using detergent-free micellar and liposomal assay .. - Metachromatic leukodystrophy: consequences of sulphatide accumulationV Gieselmann
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Bonn, Germany
Acta Paediatr Suppl 92:74-9; discussion 45. 2003b>Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide)... - Sulfatide storage in visceral organs of arylsulfatase A-deficient miceI Schott
Department of Anatomy, University of Kiel, Germany
Virchows Arch 439:90-6. 2001..of sulfatides in visceral organs and in the nervous system and leads to wide-spread demyelination (metachromatic leukodystrophy, MLD). ASA-deficient mice have previously been generated by means of targeted gene disruption... - Hyperactivity, neuromotor defects, and impaired learning and memory in a mouse model for metachromatic leukodystrophyR D'hooge
Laboratory of Neurochemistry and Behaviour, Born Bunge Foundation, and Department of Neurology Memory Clinic, University of Antwerp, Antwerp, Belgium
Brain Res 907:35-43. 2001Deficiency of arylsulfatase A (ASA) causes the autosomal recessive lipidosis, metachromatic leukodystrophy (MLD)... - Gene therapy of metachromatic leukodystrophyUlrich Matzner
Rheinische Friedrich Wilhelms Universitat, Institut fur Physiologische Chemie, Nussallee 11, D 53115 Bonn, Germany
Expert Opin Biol Ther 5:55-65. 2005b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disease that is caused by a deficiency of arylsulfatase A (ASA)... - Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cellsAlessandra Biffi
San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scienctific Institute, Milan, Italy
J Clin Invest 113:1118-29. 2004..therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD)... - Lysosomal sulfatide storage in the brain of arylsulfatase A-deficient mice: cellular alterations and topographic distributionD Wittke
Department of Anatomy, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany
Acta Neuropathol (Berl) 108:261-71. 2004..A (ASA) leads to lysosomal storage of sulfatides and to dramatic demyelination in the CNS of humans (metachromatic leukodystrophy, MLD)... - Lysosomal sulfoglycolipid storage in the kidneys of mice deficient for arylsulfatase A (ASA) and of double-knockout mice deficient for ASA and galactosylceramide synthaseR Lullmann-Rauch
Department of Anatomy, University of Kiel, Olshausenstrasse 40, 24098 Kiel, Germany
Histochem Cell Biol 116:161-9. 2001..lysosomal accumulation of sulfoglycolipids (mainly sulfo-galactosylceramide, S-GalCer ) and leads to metachromatic leukodystrophy in humans. Among visceral organs, kidneys are particularly affected... - Bone marrow stem cell-based gene transfer in a mouse model for metachromatic leukodystrophy: effects on visceral and nervous system disease manifestationsU Matzner
, , Bonn, Germany
Gene Ther 9:53-63. 2002Arylsulfatase A (ASA) knockout mice represent an animal model for the lysosomal storage disease metachromatic leukodystrophy (MLD)... - Neuromotor alterations and cerebellar deficits in aged arylsulfatase A-deficient transgenic miceR D'hooge
Laboratory of Neurochemistry and Behavior at Born Bunge Foundation, University of Antwerp1, Belgium
Neurosci Lett 273:93-6. 1999..mice and ASA(+/+) controls were constructed as a transgenic model for the lysosomal storage disease, metachromatic leukodystrophy (MLD)... - Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophyB Hess
Institut für Biochemie II, Georg August Universitat Gottingen, Federal Republic of Germany
Proc Natl Acad Sci U S A 93:14821-6. 1996b>Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms... - Morphological alterations in the inner ear of the arylsulfatase A-deficient mouseR Coenen
Department of Anatomy, University of Kiel, Germany
Acta Neuropathol 101:491-8. 2001b>Metachromatic leukodystrophy of humans is an inherited sulfatide lipidosis due to deficiency of arylsulfatase A (ASA). As an animal model, ASA(-/-) mice have been generated... - Importance of the glycosylation and polyadenylation variants in metachromatic leukodystrophy pseudodeficiency phenotypeJ S Harvey
Department of Chemical Pathology, Women s and Children s Hospital, North Adelaide, 5006, Australia
Hum Mol Genet 7:1215-9. 1998b>Metachromatic leukodystrophy (MLD) is an inborn error of myelin metabolism caused by a deficiency of the lysosomal hydrolase, arylsulfatase A (ASA)... - Decline in brainstem auditory-evoked potentials coincides with loss of spiral ganglion cells in arylsulfatase A-deficient miceR D'hooge
Laboratory of Neurochemistry and Behaviour, Born Bunge Foundation, and Memory Clinic, Neurology Department, Middelheim Hospital, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium
Brain Res 847:352-6. 1999..A (ASA)-deficient mice constitute an animal model for the inherited lysosomal storage disease, metachromatic leukodystrophy (MLD)... - Coexpression of formylglycine-generating enzyme is essential for synthesis and secretion of functional arylsulfatase A in a mouse model of metachromatic leukodystrophyYukiko Takakusaki
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan
Hum Gene Ther 16:929-36. 2005b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder involving inherited deficiency of arylsulfatase A (ASA)... - Specific downregulation and mistargeting of the lipid raft-associated protein MAL in a glycolipid storage disorderK Saravanan
Institute of Physiological Chemistry, Rheinische Friedrich Wilhelms Universitat, Bonn, Germany
Neurobiol Dis 16:396-406. 2004b>Metachromatic leukodystrophy (MLD) is a lysosomal lipid storage disease caused by arylsulfatase A deficiency. In MLD patients the sphingolipid sulfatide increasingly accumulates leading to progressive demyelination... - Three novel mutant arylsulfatase A alleles causing metachromatic leukodystrophyAfshin Yaghootfam
Institute of Physiological Chemistry, , Nussallee 11, 53115 Bonn, Germany
Neurochem Res 29:933-42. 2004b>Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. This leads to the accumulation of 3-O-sulfogalactosylceramide, which results in severe demyelination... - Late onset MLD with normal nerve conduction associated with two novel missense mutations in the ASA geneS Gallo
Istituto BIRD Europe, Vicenza, Italy
J Neurol Neurosurg Psychiatry 75:655-7. 2004b>Metachromatic leukodystrophy (MLD) rarely has its clinical onset in young adults, with a combination of cognitive and behavioural symptoms and peripheral neuropathy... - [Lysosomal diseases [metachromatic leukodystrophy (adult), Krabbe's disease (adult)]]Masaru Kuriyama
Second Department of Internal Medicine, Fukui Medical University
Nippon Rinsho 62:393-8. 2004 - High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophyJ Kreysing
Department of Biochemistry II, Georg August Universitat, Gottingen, Germany
Am J Hum Genet 53:339-46. 1993We identified a patient suffering from late-infantile metachromatic leukodystrophy (MLD) who has a residual arylsulfatase A (ARSA) activity of about 10%... - Novel mutations in arylsulfatase A gene in three Ukrainian families with metachromatic leukodystrophyNatalia V Olkhovich
Department of Medical Genetics, Kyiv Medical Academy of Postdiploma Education, Kyiv, Ukraine
Mol Genet Metab 80:360-3. 2003b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA) or saposin B. The majority of mutations identified in patients with MLD are unique within individual families... - Intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophyCaroline Sevin
Institut National de la Santé et de la Recherche Médicale U561, Universite Paris V, 75014 Paris, France
Hum Mol Genet 15:53-64. 2006b>Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal disease caused by a defect of the enzyme arylsulfatase A (ARSA) that disrupts the degradation of sulfatides (Sulf) in neurons and glial cells... - Metachromatic leukodystrophy: recent research developmentsVolkmar Gieselmann
Institute of Physiological Chemistry, Rheinische Friedrich Wilhelms Universitat Bonn, Bonn, Germany
J Child Neurol 18:591-4. 2003b>Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A, causing the storage of the sphingolipid sulfatide... - Non-inhibitory antibodies impede lysosomal storage reduction during enzyme replacement therapy of a lysosomal storage diseaseUlrich Matzner
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Nussallee 11, D 53115 Bonn, Germany
J Mol Med (Berl) 86:433-42. 2008..We reported previously that treatment of a knockout mouse model of the sphingolipid storage disease metachromatic leukodystrophy (MLD) by intravenous injection of recombinant human arylsulfatase A (rhASA) reduces sulfatide storage .. - Structure of the mouse arylsulfatase A gene and cDNAJ Kreysing
Department of Biochemistry II, Georg August Universitat Gottingen, Federal Republic of Germany
Genomics 19:249-56. 1994..The coding sequence has 1518 nucleotides and predicts a protein of 506 amino acids. The nucleotide as well as the amino acid sequence is highly conserved among humans and mice... - Novel mutations associated with metachromatic leukodystrophy: phenotype and expression studies in nine Czech and Slovak patientsLinda Berna
Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic
Am J Med Genet A 129:277-81. 2004b>Metachromatic leukodystrophy (MLD) is an inherited demyelinating disorder caused by the deficiency of arylsulphatase A (ASA)... - Atypical clinical course in juvenile metachromatic leukodystrophy involving novel arylsulfatase A gene mutationsBanu Anlar
Hacettepe University Faculty of Medicine, Department of Paediatric Neurology, Ankara, Turkey
Dev Med Child Neurol 48:383-7. 2006A male and female with juvenile metachromatic leukodystrophy (MLD) with unusual manifestations are presented, each involving a novel arylsulfatase A gene mutation... - Sulfatide with short fatty acid dominates in astrocytes and neuronsGiorgis Isaac
Department of Analytical Chemistry, Uppsala University, Sweden
FEBS J 273:1782-90. 2006..the molecular species of sulfatide in cultured astrocytes and a mouse model of the human disease metachromatic leukodystrophy. In these arylsulfatase A (ASA)-deficient mice sulfatide accumulates intracellularly in neurons and .. - Reduced brain cholesterol content in arylsulfatase A-deficient miceDieter Lutjohann
Institute of Clinical Pharmacology, University of Bonn, Germany
Biochem Biophys Res Commun 344:647-50. 2006b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by deficiency in arylsulfatase A (ASA)... - Adult onset metachromatic leukodystrophy without electroclinical peripheral nervous system involvement: a new mutation in the ARSA geneAna M Marcão
Institute of Physiological Chemistry, University of Bonn, Bonn, Germany
Arch Neurol 62:309-13. 2005b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by the deficiency of arylsulfatase A (ARSA)... - Ex vivo cell-mediated gene therapy for metachromatic leukodystrophy using neurospheresKen Kawabata
Department of Biochemistry and Molecular Biology, Nippon Medical School, Japan
Brain Res 1094:13-23. 2006b>Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by mutations in the gene encoding the lysosomal enzyme arylsulfatase A (ASA)... - Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophyMaria I Givogri
Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy
J Neurosci 26:3109-19. 2006..cell therapy for presymptomatic arylsulfatase A (ARSA) null neonate mice, a murine model for human metachromatic leukodystrophy (MLD)... - Axons mediate the distribution of arylsulfatase A within the mouse hippocampus upon gene deliveryTonia Luca
Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy
Mol Ther 12:669-79. 2005..an additional mechanism of enzyme distribution after in vivo brain gene transfer in an animal model of metachromatic leukodystrophy (MLD)... - Homozygote for mutation c.1204 + 1G > A of the ARSA gene presents with a late-infantile form of metachromatic leukodystrophy and a rare MRI white matter lesion typeAgnieszka Ługowska
Institute of Psychiatry and Neurology, Department of Genetics, Al Sobieskiego 9, 02 957 Warsaw, Poland
J Appl Genet 46:337-9. 2005The metachromatic leukodystrophy (MLD)--causing mutation c.1204 + 1G > A damages an intron-exon splice site recognition sequence. This results in a complete loss of enzymatic activity of arylsulfatase A (ARSA) protein molecules... - Modest phenotypic improvements in ASA-deficient mice with only one UDP-galactose:ceramide-galactosyltransferase geneS Franken
Department of Physiological Chemistry, University of Bonn, Germany
Lipids Health Dis 5:21. 2006Arylsulfatase A (ASA)-deficient mice are a model for the lysosomal storage disorder metachromatic leukodystrophy. This lipidosis is characterised by the lysosomal accumulation of the sphingolipid sulfatide... - Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in miceAlessandra Biffi
San Raffaele Telethon Institute for Gene Therapy, Vita Salute San Raffaele University, Milan, Italy
J Clin Invest 116:3070-82. 2006b>Metachromatic leukodystrophy (MLD) is a demyelinating lysosomal storage disorder for which new treatments are urgently needed... - Juvenile metachromatic leukodystrophyK De Prest
Department of Radiology, UZ Gent, Gent, Belgium
JBR-BTR 90:182-3. 2007 - Isolated peripheral neuropathy in atypical metachromatic leukodystrophy: a recurrent mutationMarion B Coulter-Mackie
Department of Pediatrics, University of British Columbia, Vancouver, Canada
Can J Neurol Sci 29:159-63. 2002BACKGROUND: Metachromatic leukodystrophy (MLD) is a genetic neurodegenerative disorder resulting from a deficiency of arylsulfatase A. Late onset forms are relatively rare... - Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do not influence enzyme activityG D Georgeson
Mullikin Medical Centers, Artesia, CA, USA
Bone Marrow Transplant 29:487-90. 2002..Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery... - Early signs of neurolipidosis-related behavioural alterations in a murine model of metachromatic leukodystrophyStijn Stroobants
Laboratory of Biological Psychology, Department of Psychology, University of Leuven, Leuven, Belgium
Behav Brain Res 189:306-16. 2008Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal storage disorder metachromatic leukodystrophy (MLD)... - Retrovirally expressed human arylsulfatase A corrects the metabolic defect of arylsulfatase A-deficient mouse cellsU Matzner
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Nussallee 11, 53115 Bonn, Germany
Gene Ther 7:805-12. 2000A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy (MLD) which is characterized primarily by demyelination of the central nervous system... - Reduced intensity conditioning haematopoietic stem cell transplantation with mesenchymal stromal cells infusion for the treatment of metachromatic leukodystrophy: a case reportN Meuleman
Department of Clinical and Experimental Hematology, Institut Jules Bordet, Universite Libre de Bruxelles ULB, Bruxelles, Belgium
Haematologica 93:e11-3. 2008We report the case of a 23-year-old woman who presented with an adult form of metachromatic leukodystrophy (MLD) evolving over one year with a progressive neurological deterioration... - Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophiesYanli Cui
Departement de Chimie, Ecole Normale Superieure, UMR 8642, CNRS ENS UPMC, 24 rue Lhomond, 75231 Paris Cedex 05, France
Glycoconj J 25:147-55. 20083-O-Sulfogalactosylceramides (sulfatides) accumulate in the genetic disease metachromatic leukodystrophy which is due to a defect in the catabolic enzyme, arylsulfatase A... - Induction of tolerance to human arylsulfatase A in a mouse model of metachromatic leukodystrophyUlrich Matzner
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Nussallee 11, D 5315 Bonn, Germany
Mol Med 13:471-9. 2007A deficiency of arylsulfatase A (ASA) causes metachromatic leukodystrophy (MLD), a lysosomal storage disorder characterized by accumulation of sulfatide, a severe neurological phenotype and early death... - Adult-onset MLD: a gene mutation with isolated polyneuropathyK J Felice
Department of Neurology, University of Connecticut School of Medicine, Farmington 06035 1840, USA
Neurology 55:1036-9. 2000..Results of studies of CNS integrity, including cranial MRI, evoked potentials, and neuropsychologic tests, were normal. Molecular genetic analyses revealed a novel homozygous missense mutation (Thr286Pro) in the ASA gene... - Investigations of micro-organic brain damage (MOBD) in heterozygotes of metachromatic leukodystrophyAnna Tylki-Szymanska
Memorial Institute Child Health Centre, Department of Metabolic Diseases, Warsaw, Poland
Am J Med Genet 110:315-9. 2002..expressed as micro-organic brain damage (MOBD) was investigated in 27 unrelated heterozygotes with metachromatic leukodystrophy (MLD)... - Partial cure of established disease in an animal model of metachromatic leukodystrophy after intracerebral adeno-associated virus-mediated gene transferC Sevin
Institut National de la Santé et de la Recherche Médicale Inserm U745, Laboratory of Molecular Genetics and Université ParisV, Paris, France
Gene Ther 14:405-14. 2007b>Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by genetic deficiency of arylsulfatase A (ARSA) enzyme... - Stabilization of juvenile metachromatic leukodystrophy after bone marrow transplantation: a 13-year follow-upMaria Görg
Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
J Child Neurol 22:1139-42. 2007A 29-year-old female patient with juvenile metachromatic leukodystrophy diagnosed at age 14 years received a bone marrow transplant at age 16 years... - Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophagesNicole Muschol
Children's Hospital, University of Hamburg, Martinistr. 52, D-20246 Hamburg, Germany
Biochem J 368:845-53. 2002..The data suggest that other mechanisms than the proposed M6P-dependent secretion/recapture of lysosomal enzymes might be responsible for therapeutic effects of bone marrow transplantation in the brain... - Sperm surface arylsulfatase A can disperse the cumulus matrix of cumulus oocyte complexesAlexander Wu
Hormones Growth Development Research Group, Ottawa Health Research Institute, Ottawa, Ontario, Canada
J Cell Physiol 213:201-11. 2007.... - A spontaneously immortalized Schwann cell line to study the molecular aspects of metachromatic leukodystrophyKarumbayaram Saravanan
Institut fur Physiologische Chemie, Rheinische Friedrich Wilhelms Universitat, Nussallee 11, 53115 Bonn, Germany
J Neurosci Methods 161:223-33. 2007The arylsulfatase A (ASA)-deficient mouse is a murine model of human metachromatic leukodystrophy (MLD) caused by a genetic defect in the ASA gene... - Nine-year-old girl presenting familial occurrence of progressive developmental abnormalities with the white matter lesionsMasaharu Hayashi
Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan
Neuropathology 22:350-2. 2002 - Safety of arylsulfatase A overexpression for gene therapy of metachromatic leukodystrophyA Capotondo
San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy
Hum Gene Ther 18:821-36. 2007Successful gene therapy approaches for metachromatic leukodystrophy (MLD), based either on hematopoietic stem/progenitor cells (HSPCs) or direct central nervous system (CNS) gene transfer, highlighted a requirement for high levels of .. - [Metachromatic leukodystrophy in adult patient initially diagnosed as multiple sclerosis]Zofia Kazibutowska
Kliniki Neurologii SlAM w Katowicach
Neurol Neurochir Pol 36:1209-19. 2002..Therefore, it was decided to assay arylsulphatase A activity. The result confirmed the diagnosis of the late onset MLD. Additionally, molecular genetic examination was performed of a DNA sample obtained from the patient... - Sphingolipidoses in TurkeyHatice Asuman Ozkara
Department of Biochemistry, Hacettepe University Faculty of Medicine, 06100 Ankara, Turkey
Brain Dev 26:363-6. 2004..of 300 patients (15%) with sphingolipidoses were diagnosed; there were deficiencies of arylsulfatase A [metachromatic leukodystrophy (MLD)] in 93 (31%), hexosaminidase [Sandhoff disease (SHD)] in 62 (20... - Structural analysis of the mouse prosaposin (SGP-1) gene reveals the presence of an exon that is alternatively spliced in transcribed mRNAsQ Zhao
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
Mol Reprod Dev 48:1-8. 1997..The deficiency of saposins B and C results in variant forms of metachromatic leukodystrophy and Gaucher's disease, respectively, which are characterized by lysosomal storage of undegraded .. - Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidosesKyoko Suzuki
Department of Psychiatry, Yokohama City University School of Medicine, 3 9 Fukuura, Kanazawa Ku, Yokohama, 236 0004, Japan
Acta Neuropathol 114:481-9. 2007..we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay-Sachs disease, metachromatic leukodystrophy, beta-galactosialidosis and adrenoleukodystrophy, for the expression of alpha- and beta-synucleins and .. - Identification of diffuse and focal brain lesions by clinical magnetic resonance spectroscopyPeter B Kingsley
Department of Radiology, North Shore University Hospital, 300 Community Drive, Manhasset, NY 11030, USA
NMR Biomed 19:435-62. 2006..disease (globoid cell leukodystrophy), Leigh's disease, megalencephalic leukoencephalopathy with cysts, metachromatic leukodystrophy (MLD), Pelizaeus-Merzbacher disease, Zellweger syndrome, HIV-associated lesions [cryptococcus, lymphoma,.. - The frequency of lysosomal storage diseases in The NetherlandsB J Poorthuis
Dept of Pediatrics and Clinical Genetics, Leiden University of Medical Center, The Netherlands
Hum Genet 105:151-6. 1999..0 per 100,000 live births, representing 17% of all diagnosed cases. Within the group of lipidoses, metachromatic leukodystrophy (MLD) is the most frequent LSD... - Diffusion magnetic resonance imaging patterns in metabolic and toxic brain disordersR N Sener
Department of Radiology, Ege University Hospital, Bornova, Izmir, Turkey
Acta Radiol 45:561-70. 2004..To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI)... - Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseasesS Morimoto
Department of Neurosciences, University of California, San Diego, La Jolla 92093
Proc Natl Acad Sci U S A 87:3493-7. 1990..Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-.. - Arylsulfatase a gene polymorphisms in relapsing remitting multiple sclerosis: genotype-phenotype correlation and estimation of disease progressionKoraljka Bacić Baronica
Sveti Duh General Hospital, Department of Neurology, Zagreb, Croatia
Coll Antropol 35:11-6. 2011..Progressive demyelination occurs in metachromatic leukodystrophy (MLD), while the condition of ASA-pseudodeficiency (ASA-PD) is suggested to contribute to complex .. - Genetic counseling and prenatal diagnosis in India--experience at Sir Ganga Ram HospitalI C Verma
Department of Genetic Medicine, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060
Indian J Pediatr 70:293-7. 2003..Among neurolipidosis metachromatic leukodystrophy was the commonest, followed by Krabbe's disease, Tay Sach disease and Gaucher disease... - Globoid cell leukodystrophy (Krabbe's disease): updateKunihiko Suzuki
Neuroscience Center, Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
J Child Neurol 18:595-603. 2003..It is one of the two classic genetic leukodystrophies, together with metachromatic leukodystrophy. The mode of inheritance is autosomal recessive... - Role of prosaposin in the male reproductive system: effect of prosaposin inactivation on the testis, epididymis, prostate, and seminal vesiclesC R Morales
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
Arch Androl 44:173-86. 2000..The deficiency of saposins B and C results in variant forms of metachromatic leukodystrophy and Gaucher's disease, respectively, which are characterized by lysosomal storage of undegraded .. - Imaging of white matter lesionsFrederik Barkhof
Department of Radiology, Vrije University Medical Centre, Amsterdam, The Netherlands
Cerebrovasc Dis 13:21-30. 2002..The leukodystrophies that can present in adult age include metachromatic leukodystrophy, globoid cell leukodystrophy, adrenomyeloneuropathy, mitochondrial disorders, vanishing white matter, .. - Multiple sulfatase deficiency: clinical report and description of two novel mutations in a Brazilian patientOsvaldo Alfonso Artigalás
Postgraduate Program in Genetics and Molecular Biology, Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Metab Brain Dis 24:493-500. 2009..e., mucopolysaccharidosis II, IIIA, IIID, IVA and VI, metachromatic leukodystrophy, X-linked ichthyosis, and the X-linked recessive form of chondrodysplasia punctata... - [Nasu Hakola disease: a report of the first two cases in Bolivia]M C Molina-Monasterios
Servicio de Neurologia y Neurocirugia, Hospital Obrero N 1 de la Caja Nacional de Salud, La Paz, Bolivia
Rev Neurol 36:837-40. 2003..At the same time this also allows it to be distinguished from multiple sclerosis, metachromatic leukodystrophy, Marchafava Bignami disease, and prion diseases (such as new variant Creutzfeldt Jakob). - Neurometabolic diseaseH W Moser
Kennedy Krieger Institute, Baltimore, MD 21205, USA
Curr Opin Neurol 11:91-5. 1998..Animal models have been developed for X-linked adrenoleukodystrophy, metachromatic leukodystrophy and Zellweger syndrome and will aid in the understanding of pathogenesis and the evaluation of therapy. - Recombinant adeno-associated virus (rAAV) vectors for somatic gene therapy: recent advances and potential clinical applicationsM Hallek
Laboratorium für Molekulare Biologie, Genzentrum, Ludwig Maximilians Universitat, Munchen, Germany
Cytokines Mol Ther 2:69-79. 1996..Fanconi anemia, chronic granulomatous disease, Gaucher disease, metachromatic leukodystrophy and cystic fibrosis, and of acquired diseases, such as HIV infection and non-Hodgkin lymphoma... - Subacute sclerosing panencephalitis (SSPE): an insight into the diagnostic errors from a tertiary care university hospitalL K Prashanth
Department of Neurology and Department of Neurovirology, National Institute of Mental Health and Neurosciences NIMHANS, Bangalore, India
J Child Neurol 22:683-8. 2007..8%). These included seizures, absence seizures, metachromatic leukodystrophy, Schilder's disease, cerebral palsy, hemiparkinsonism, Wilson's disease, vasculitis, spinocerebellar .. - Screening patients referred to a metabolic clinic for lysosomal storage disordersMaria Fuller
Lysosomal Diseases Research Unit, SA Pathology at Women s and Children s Hospital, 72 King William Road, North Adelaide, SA 5006, Australia
J Med Genet 48:422-5. 2011..Lysosomal protein profiling is being developed as a high throughput method to screen populations for lysosomal storage disorders (LSD)... - Long-term adaptive functioning outcomes of children with inherited metabolic and genetic diseases treated with hematopoietic stem cell transplantation in a single large pediatric center: parents' perspectiveAdam Gassas
Division of Haematology Oncology BMT, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
J Pediatr Hematol Oncol 33:216-20. 2011..Hurler syndrome, 8 for malignant infantile osteopetrosis, 6 for X-linked adrenoleukodystrophy, 2 for metachromatic leukodystrophy, 2 for Gaucher disease, 1 for Ganglioside Monosialic Acid (GM) gangliosidosis, 1 for sialiosis (type 2),.. - Mucin-containing Rokitansky-Aschoff sinuses with extracellular mucin deposits simulating mucinous carcinoma of the gallbladderJorge Albores-Saavedra
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
Am J Surg Pathol 33:1633-8. 2009..He was later diagnosed with metachromatic leukodystrophy. The remaining 4 patients complained of right upper quadrant pain and had a thickened gallbladder wall .. - SUMF1 enhances sulfatase activities in vivo in five sulfatase deficienciesAlessandro Fraldi
Telethon Institute of Genetics and Medicine TIGEM, Via P Castellino, 111, 80131 Naples, Italy
Biochem J 403:305-12. 2007..e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]... - Pathological study of mice with total deficiency of sphingolipid activator proteins (SAP knockout mice)Y Oya
Department of Pathology and Laboratory Medicine, School of Medicine, University of North Carolina at Chapel Hill, 27599 7525, USA
Acta Neuropathol 96:29-40. 1998..Sap-B deficiency causes a variant of metachromatic leukodystrophy and sap-C deficiency causes a variant of Gaucher disease...
Research Grants
- CHEMICAL PATHOLOGY OF NEUROLOGICAL DISORDERSKunihiko Suzuki; Fiscal Year: 1993..neurological disorders, -- GM1-gangliosidosis/ Morquio B disease (acid beta-galactosidase deficiency), metachromatic leukodystrophy-like and Gaucher-like syndromes-(SAP-1 and SAP-2 deficiencies respectively), and a unique pleomorphic ..
- CHEMICAL PATHOLOGY OF NEUROLOGICAL DISORDERSKunihiko Suzuki; Fiscal Year: 1999..neurological disorders, -- GM1-gangliosidosis/ Morquio B disease (acid beta-galactosidase deficiency), metachromatic leukodystrophy-like and Gaucher-like syndromes-(SAP-1 and SAP-2 deficiencies respectively), and a unique pleomorphic ..
- MULTIPLEX ANALYSIS OF INBORN ERRORS OF METABOLISMFRANTISEK contact TURECEK; Fiscal Year: 2010..The proposed research aims at the detection of syndromes of Hunter, Maroteaux-Lamy, Morquio A, Metachromatic Leukodystrophy, and Sanfilippo A-D using dried blood spots on newborn screening cards...
- MULTIPLEX ANALYSIS OF INBORN ERRORS OF METABOLISMFrantisek Turecek; Fiscal Year: 2007..LSD) belonging to the Mucopolysaccharidosis groups II (MPS-II, Hunter), MPSVI (Maroteaux-Lamy), and metachromatic leukodystrophy, using dried blood spots on newborn screening cards as the enzyme source...
- MULTIPLEX ANALYSIS OF INBORN ERRORS OF METABOLISMFrantisek Turecek; Fiscal Year: 2007..LSD) belonging to the Mucopolysaccharidosis groups II (MPS-II, Hunter), MPS- VI (Maroteaux-Lamy), and metachromatic leukodystrophy, using dried blood spots on newborn screening cards as the enzyme source...
- Imaging the Pathophysiology of AMN in Mice and HumansFlorian Eichler; Fiscal Year: 2007..Ultimately, insights gained in these studies of ALD/AMN may prove beneficial to other neurodegenerative diseases, such as amyotrophic lateral sclerosis or Parkinson's and Alzheimer's diseases. ..
- MODULATION OF PRB2/P130 MEDIATED GROWTH SUPPRESSIONAntonio Giordano; Fiscal Year: 2002..To understand the regulatory function of pRb2/p130 phosphorylation, c. To define the role of the Rb2/p130 gene in human lung cancer development and progression, d. To prepare viral models for studying pRB2/p130 in vivo. ..
- CNS DEFECT IN A MURINE ZELLWEGER SYNDROME MODELPhyllis Faust; Fiscal Year: 2002....
- Interaction between HIV-1 and cell cycle proteinsAntonio Giordano; Fiscal Year: 2003..In particular, we will focus our attention on the cell cycle regulatory proteins, pRb2/pl30, Cdk9 and cycT1, which seem to be involved in AIDS-related tumorigenesis. ..
- Functional Language Organization in Childhood StrokeANNA BYARS; Fiscal Year: 2006..The findings will contribute to the understanding of brain plasticity, language development, and assessment and treatment of language disorders. ..
- CNS defects in a murine Zellweger syndrome modelPhyllis Faust; Fiscal Year: 2007....