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Metachromatic Leukodystrophy (Sulfatide Lipidosis)

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An autosomal recessive metabolic disease caused by a deficiency of CEREBROSIDE-SULFATASE leading to intralysosomal accumulation of cerebroside sulfate (SULFOGLYCOSPHINGOLIPIDS) in the nervous system and other organs. Pathological features include diffuse demyelination, and metachromatically-staining granules in many cell types such as the GLIAL CELLS. There are several allelic and nonallelic forms with a variety of neurological symptoms.

Also Known As:

Sulfatide Lipidosis; Leukodystrophy, Metachromatic; Arylsulfatase A Deficiency; Cerebral sclerosis, Diffuse, Metachromatic Form; Cerebroside Sulfatase Deficiency; Greenfield Disease; Greenfield's Disease; Leukodystrophy, Metachromatic, Adult; Leukodystrophy, Metachromatic, Juvenile; Metachromatic Leukodystrophy, Adult-Type; Metachromatic Leukodystrophy, Infant; Metachromatic Leukodystrophy, Infant-Type; Metachromatic Leukodystrophy, Juvenile-Type; Metachromatic Leukoencephalopathy; Adult-Type Metachromatic Leukodystrophies; Adult-Type Metachromatic Leukodystrophy; Arylsulfatase A Deficiencies; Cerebroside Sulfatase Deficiencies; Deficiencies, Arylsulfatase A; Deficiencies, Cerebroside Sulfatase; Deficiency, Arylsulfatase A; Deficiency, Cerebroside Sulfatase; Infant Metachromatic Leukodystrophies; Infant Metachromatic Leukodystrophy; Infant-Type Metachromatic Leukodystrophies; Infant-Type Metachromatic Leukodystrophy; Juvenile-Type Metachromatic Leukodystrophies; Juvenile-Type Metachromatic Leukodystrophy; Leukodystrophies, Adult-Type Metachromatic; Leukodystrophies, Juvenile-Type Metachromatic; Leukodystrophies, Metachromatic; Leukodystrophy, Adult-Type Metachromatic; Leukodystrophy, Juvenile-Type Metachromatic; Leukoencephalopathies, Metachromatic; Leukoencephalopathy, Metachromatic; Lipidosis, Sulfatide; Metachromatic Leukodystrophies; Metachromatic Leukodystrophies, Adult-Type; Metachromatic Leukodystrophies, Infant; Metachromatic Leukodystrophies, Infant-Type; Metachromatic Leukodystrophies, Juvenile-Type; Metachromatic Leukodystrophy, Adult Type; Metachromatic Leukodystrophy, Infant Type; Metachromatic Leukodystrophy, Juvenile Type; Metachromatic Leukoencephalopathies; Sulfatase Deficiencies, Cerebroside; Sulfatase Deficiency, Cerebroside; Arylsulfatase A Deficiency Disease; Cerebroside Sulphatase Deficiency Disease

Networked: 428 relevant articles (15 outcomes, 24 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Globoid Cell Leukodystrophy (Krabbe Disease)
2.	Adrenoleukodystrophy (Adrenoleukodystrophy, X-Linked)
3.	Gaucher Disease (Gaucher's Disease)
4.	Mucopolysaccharidoses
5.	Fucosidosis

Experts

1.	Gieselmann, Volkmar: 29 articles (09/2015 - 01/2003)
2.	Gieselmann, V: 15 articles (02/2010 - 03/2000)
3.	Matzner, Ulrich: 13 articles (09/2015 - 01/2005)
4.	Eckhardt, Matthias: 8 articles (09/2015 - 06/2006)
5.	Fogh, Jens: 8 articles (06/2012 - 05/2005)
6.	D'Hooge, Rudi: 7 articles (07/2015 - 09/2007)
7.	Lüllmann-Rauch, R: 7 articles (01/2006 - 05/2001)
8.	Stroobants, Stijn: 6 articles (07/2015 - 06/2008)
9.	Aubourg, Patrick: 6 articles (06/2015 - 01/2006)
10.	Matthes, Frank: 6 articles (06/2012 - 09/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Metachromatic Leukodystrophy:

1.	Cerebroside-Sulfatase (Arylsulfatase A)IBA 07/01/1972 - "An improved method for the determination of leukocyte arylsulfatase A and its application to the diagnosis of metachromatic leukodystrophy in homozygous and heterozygous states." 05/20/2011 - "Preclinical studies in mouse models of metachromatic leukodystrophy, however, showed that arylsulfatase A (ASA) is able to cross the BBB to some extent, thus reducing lysosomal storage in brain microglial cells. " 12/01/2006 - "In this proof of concept study, we explore whether glial precursors derived from murine ES cells (ESGPs) and engineered to overexpress human arylsulfatase A (hASA) can cross-correct the metabolic defect in an animal model of metachromatic leukodystrophy (MLD). " 11/01/2005 - "In this multicentre study, we examined the prevalence of two mutations in the arylsulfatase A (ARSA) gene, i.e., c.459+1G>A and p.P426L, in 384 unrelated European patients presenting with different types of metachromatic leukodystrophy (MLD). " 12/23/1985 - "Studies in metachromatic leukodystrophy: XV. Purification of normal and mutant arylsulfatase A from human liver."
2.	Lysergic Acid Diethylamide (LSD)IBA 04/01/2014 - "As both the immune system and the blood-brain barrier (BBB) are likely to be developmentally immature in the perinatal period, neonatal gene transfer may be useful for the treatment of lysosomal storage disease (LSD) with neurological involvements such as metachromatic leukodystrophy (MLD). " 07/15/2011 - "Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death. " 07/01/1999 - "Within the group of lipidoses, metachromatic leukodystrophy (MLD) is the most frequent LSD. " 01/01/1993 - "In total, 363 patients with mucopolysaccharidoses (MPS), mucolipidoses, glycoproteinoses, sphingolipidoses and other LSD were diagnosed; 55 families at risk sought prenatal diagnosis and 67 fetuses were investigated for MPS (types I, II, IIIA and IIIB, VI), Tay-Sachs disease, Sandhoff disease, GM1-gangliosidosis, metachromatic leukodystrophy, mannosidosis, Gaucher disease and multiple sulphatidosis; 17 affected fetuses were diagnosed and aborted. " 01/01/2011 - "Here we describe a cell-based assay using patient cell lines to identify small molecules that enhance the residual arylsulfatase A (ASA) activity found in patients with metachromatic leukodystrophy (MLD), a progressive neurodegenerative LSD. "
3.	Sulfoglycosphingolipids (Sulfatides)IBA 02/01/1965 - "STRUCTURAL STUDIES ON SULFATIDES IN METACHROMATIC LEUKODYSTROPHY." 06/10/2014 - "Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry." 03/30/2014 - "Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy." 10/21/2013 - "Direct tandem mass spectrometric profiling of sulfatides in dry urinary samples for screening of metachromatic leukodystrophy." 01/01/2012 - "Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. "
4.	SaposinsIBA 06/01/1993 - "A human mutation in saposin B-deficient metachromatic leukodystrophy, in which its glycosylation site is eliminated, has been reported. " 08/01/2008 - "Mutations in saposin B present in humans with phenotypes resembling metachromatic leukodystrophy. " 02/01/1999 - "As an alternative to arylsulphatase A deficiency, deficiency of saposin B causes metachromatic leukodystrophy. " 02/01/1999 - "An Asn > Lys substitution in saposin B involving a conserved amino acidic residue and leading to the loss of the single N-glycosylation site in a patient with metachromatic leukodystrophy and normal arylsulphatase A activity." 07/01/1998 - "A 2-year-old child had a metachromatic leukodystrophy-variant phenotype mainly involving the peripheral nervous system (PNS) that was caused by saposin-B deficiency. "
5.	DNA (Deoxyribonucleic Acid)IBA 01/01/1994 - "The characterization of the mutations causing pseudodeficiency has allowed the detection of the pseudodeficiency allele in the DNA of probands and has thus improved the diagnosis and genetic counselling for metachromatic leukodystrophy." 01/01/2014 - "Lentivector integration sites in ependymal cells from a model of metachromatic leukodystrophy: non-B DNA as a new factor influencing integration." 02/01/1997 - "DNA-based diagnosis of arylsulfatase A deficiencies as a supplement to enzyme assay: a case in point." 04/01/1996 - "The presence of vector DNA in the brain 4 months after transplantation suggests a role for gene transfer and stem cell transplantation in the treatment strategies for metachromatic leukodystrophy." 01/01/1991 - "Therefore confirmation of a diagnosis of metachromatic leukodystrophy and Krabbe disease, as well as accurate identification of carriers, requires additional testing including 14C-sulfatide loading in cultured skin fibroblasts, examination of urine for excretion of undegraded lipids, examination of enzyme levels in additional family members including grandparents, and molecular analysis of DNA samples for known mutations."
6.	Galactose (Galactopyranose)FDA LinkGeneric 09/30/1991 - "Improved synthesis of [1-14C]acyl-sphingosine-galactose-3-sulfate (sulfatide) for diagnosis of metachromatic leukodystrophy: usefulness of radioscanning." 11/01/1971 - " Analyses of cultivated amniotic fluid cells have enabled diagnoses of galactosemia (deficient galactose-1-phosphate uridyl transferase), X-linked uric aciduria (by autoradiography), lysosomal acid phosphatase deficiency, metachromatic leukodystrophy (deficientaryl sulfatase A), mucopolysaccharidosis, cystic fibrosis (metachromatic granules), and Marfan's syndrome (metachromatic granules). "
7.	Complementary DNA (cDNA)IBA 04/15/2007 - "In an effort to develop an encapsulated cell-based system to deliver arylsulfatase A (ARSA) to the central nervous system of metachromatic leukodystrophy (MLD) patients, we engineered C2C12 mouse myoblasts with a retroviral vector containing a full-length human ARSA cDNA and evaluated the efficacy of the recombinant secreted enzyme to revert the MLD phenotype in oligodendrocytes (OL) of the As2-/- mouse model. "
8.	SphingosineIBA 09/30/1991 - "Improved synthesis of [1-14C]acyl-sphingosine-galactose-3-sulfate (sulfatide) for diagnosis of metachromatic leukodystrophy: usefulness of radioscanning."
9.	Complement System Proteins (Complement)IBA 07/01/1986 - "Because of their central role in host defense (in inflammatory responses, in antigen presentation, and in immunoregulatory networks), monocyte/macrophage dysfunction may result in one or more pathophysiologic consequences: defects in monocyte maturation, deficiencies in the clearance of physiologic substrates in lysosomal diseases (e.g., Gaucher's disease, mucopolysaccharidoses, osteopetrosis, metachromatic leukodystrophy), decreased synthesis and secretion of mediators (complement component deficiencies), defects in microbicidal activity (chronic granulomatous disease) and defects which are acquired following infection and during chemotherapy (e.g., acquired immune deficiency syndrome)."
10.	ArylsulfatasesIBA 10/01/1984 - "Neither child had metachromatic leukodystrophy (MLD) and they were diagnosed as having benign pseudo arylsulfatase A deficiency trait (PD). " 10/01/1984 - "Genotype assignments in a family with the pseudo arylsulfatase a deficiency trait without metachromatic leukodystrophy." 12/01/1983 - "Thus, metachromatic leukodystrophy and pseudo arylsulfatase-A deficiency are allelic conditions. " 12/01/1983 - "Pseudo arylsulfatase-A deficiency in healthy individuals: genetic and biochemical relationship to metachromatic leukodystrophy." 01/01/1983 - "On the basis of the results, they may be classified into three groups: I, deficient in all three arylsulphatases; II, deficient only in arylsulphatases-A and -C with half or near-normal arylsulphatase-B; electrophoretically, arylsulphatase-A activity bands are undetectable as in metachromatic leukodystrophy; III, same as in II except electrophoretically, the residual arylsulphatase-A is detectable as faint activity bands similar to those in pseudo arylsulphatase-A deficiency. "

Therapies and Procedures

1.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 12/01/1998 - "Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy." 10/01/1992 - "Longitudinal neurophysiologic studies in a patient with metachromatic leukodystrophy following bone marrow transplantation." 07/01/2010 - "Successful treatment of metachromatic leukodystrophy using bone marrow transplantation of HoxB4 overexpressing cells." 09/01/2007 - "The long-term stabilization in this patient, however, suggested that bone marrow transplantation may halt the progression of juvenile metachromatic leukodystrophy." 09/01/2007 - "Data on the natural course of juvenile metachromatic leukodystrophy are rare, so in the present case it is difficult to establish whether the rather favorable course can be attributed with certainty to bone marrow transplantation. "
2.	Hematopoietic Stem Cell Transplantation 03/01/2015 - "A systematic evaluation regarding the efficacy of hematopoietic stem cell transplantation and a longer follow up period for gene therapy are needed to come to a general conclusion and improve treatment options for metachromatic leukodystrophy. " 01/01/2015 - "Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report." 01/01/2012 - "Long-term neuroimaging follow-up on an asymptomatic juvenile metachromatic leukodystrophy patient after hematopoietic stem cell transplantation: evidence of myelin recovery and ongoing brain maturation." 10/01/2008 - "Hematopoietic stem cell transplantation (HSCT) can benefit selected subsets of patients with some LSDs, but results have been poor in several other disorders, including metachromatic leukodystrophy (MLD), outlining the need for innovative therapeutic approaches in this field. " 10/01/2008 - "Hurler syndrome, metachromatic leukodystrophy, globoid-cell leukodystrophy (Krabbe's disease) and X-linked adrenoleukodystrophy are inherited diseases of the CNS that can be cured or arrested by allogeneic hematopoietic stem-cell transplantation (HSCT). "
3.	Enzyme Replacement Therapy 06/01/2012 - "Efficacy of enzyme replacement therapy in an aggravated mouse model of metachromatic leukodystrophy declines with age." 05/25/2005 - "The production of active Arylsulfatase A is a key step in the development of enzyme replacement therapy for Metachromatic Leukodystrophy. " 05/25/2005 - "Expression and purification of a human, soluble Arylsulfatase A for Metachromatic Leukodystrophy enzyme replacement therapy." 01/01/1984 - "Since partially purified preparations of galactocerebroside beta-galactosidase and homogeneous arylsulfatase A are now available, the possibility of enzyme replacement therapy in globoid and metachromatic leukodystrophies is discussed."
4.	Immunomodulation 10/01/1996 - "Neuropathy of metachromatic leukodystrophy: improvement with immunomodulation." 10/01/1996 - "We conclude that immunomodulation early in the course of metachromatic leukodystrophy presenting as a neuropathy may result in temporary functional improvement. "
5.	Drug Therapy (Chemotherapy) 07/01/1986 - "Because of their central role in host defense (in inflammatory responses, in antigen presentation, and in immunoregulatory networks), monocyte/macrophage dysfunction may result in one or more pathophysiologic consequences: defects in monocyte maturation, deficiencies in the clearance of physiologic substrates in lysosomal diseases (e.g., Gaucher's disease, mucopolysaccharidoses, osteopetrosis, metachromatic leukodystrophy), decreased synthesis and secretion of mediators (complement component deficiencies), defects in microbicidal activity (chronic granulomatous disease) and defects which are acquired following infection and during chemotherapy (e.g., acquired immune deficiency syndrome)."