Disease relevance of Leukodystrophy, Metachromatic

• Diagnosis of metachromatic leukodystrophy, Krabbe disease, and Farber disease after uptake of fatty acid-labeled cerebroside sulfate into cultured skin fibroblasts [1].
• A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy, which is characterized by accumulation of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide) [2].
• Late infantile metachromatic leukodystrophy (MLD) is a neurodegenerative disease, most commonly caused by the deficiency of the lysosomal enzyme arylsulfatase A (ARSA) [3].
• The present review focuses on recent developments in X-linked adrenoleukodystrophy, Alexanders disease, Canavans disease, metachromatic leukodystrophy, globoid cell leukodystrophy (Krabbes disease) and Pelizaeus-Merzbacher disease, and briefly discusses new data on six other rare inherited leukodystrophies [4].
• Inherited deficiency for the lysosomal enzyme arylsulfatase A (ASA) leads to lysosomal storage of sulfatides and to dramatic demyelination in the CNS of humans (metachromatic leukodystrophy, MLD) [5].

Psychiatry related information on Leukodystrophy, Metachromatic

• Dementia with impaired temporal glucose metabolism in late-onset metachromatic leukodystrophy [6].

High impact information on Leukodystrophy, Metachromatic

• To understand the molecular basis of the different forms of the disease, we analyzed arylsulfatase A alleles associated with metachromatic leukodystrophy [7].
• Metabolism of cerebroside sulfate and subcellular distribution of its metabolites in cultured skin fibroblasts from controls, metachromatic leukodystrophy, and globoid cell leukodystrophy [8].
• With pulse-chase study of 1-[14C]stearic acid-labeled cerebroside sulfate (14C-CS) and subsequent subcellular fractionation by Percoll gradient, the metabolism of CS and translocation of its metabolites in human skin fibroblasts from controls, metachromatic leukodystrophy (MLD), and globoid cell leukodystrophy (GLD) were studied [8].
• Phenotype of arylsulfatase A-deficient mice: relationship to human metachromatic leukodystrophy [9].
• To analyze the genetic abnormality in a Japanese patient with adult-type metachromatic leukodystrophy (MLD), we first elucidated the genomic organization of the human arylsulfatase A (ASA) gene and then compared the nucleotide sequences of exons and splice junctions of the mutant ASA gene to those of a normal control [10].

Chemical compound and disease context of Leukodystrophy, Metachromatic

• Sulfatide excretion in metachromatic leukodystrophy [11].
• Heterogeneity in late-onset metachromatic leukodystrophy. Effect of inhibitors of cysteine proteinases [12].
• Coexpression of formylglycine-generating enzyme is essential for synthesis and secretion of functional arylsulfatase A in a mouse model of metachromatic leukodystrophy [13].
• Lysosulfatide (galactosylsphingosine-3-O-sulfate) from metachromatic leukodystrophy and normal human brain [14].
• Psychotic states induced by phencyclidine and the adult form of metachromatic leukodystrophy, as well as neurometabolic studies, suggest that schizophrenia reflects a breakdown in communication between cortical areas [15].

Biological context of Leukodystrophy, Metachromatic

• Identification of 12 novel mutations and two new polymorphisms in the arylsulfatase A gene: haplotype and genotype-phenotype correlation studies in Spanish metachromatic leukodystrophy patients [16].
• The 8 ARSA exons and adjacent intron boundaries from a patient with late-infantile metachromatic leukodystrophy were polymerase chain reaction (PCR) amplified in seven discrete reactions [17].
• An arylsulfatase A (ARSA) missense mutation (T274M) causing late-infantile metachromatic leukodystrophy [17].
• Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of a patient affected with late infantile metachromatic leukodystrophy revealed that the patient is a compound heterozygote of two alleles carrying two deleterious mutation each [18].
• Brainstem auditory evoked responses (BAERs) were recorded in seven patients with Pelizaeus-Merzbacher leukodystrophy (PMD), two with adrenoleukodystrophy (ALD), and one with metachromatic leukodystrophy (MLD) [19].

Anatomical context of Leukodystrophy, Metachromatic

• Metachromatic leukodystrophy is due to deficient activity of arylsulfatase A, an enzyme important in myelin catabolism [20].
• Late infantile metachromatic leukodystrophy (MLD) was successfully diagnosed in utero by demonstrating the absence of arylsulfatase-A in amniotic fluid using diethylaminoethyl-Sepharose column chromatography [21].
• The AB-variant of metachromatic leukodystrophy (postulated activator protein deficiency). Light and electron microscopic findings in a sural nerve biopsy [22].
• Measurements from normal umbilical cord blood of four lysosomal enzymatic activities: alpha-L-iduronidase (Hurler), galactocerebrosidase (globoid cell leukodystrophy), arylsulfatase A (metachromatic leukodystrophy), arylsulfatase B (Maroteaux-Lamy) [23].
• Trials of bone marrow transplantation are being pursued for metachromatic leukodystrophy and adrenoleukodystrophy [24].

Gene context of Leukodystrophy, Metachromatic

• High residual arylsulfatase A (ARSA) activity in a patient with late-infantile metachromatic leukodystrophy [25].
• While most patients with metachromatic leukodystrophy have mutations in the gene for arylsulfatase A, some patients have deficient SAP-1, as determined by immunological techniques [26].
• Insertion in the mRNA of a metachromatic leukodystrophy patient with sphingolipid activator protein-1 deficiency [26].
• While most patients with metachromatic leukodystrophy have defects in arylsulfatase A, some patients have defects in SAP-1 [27].
• Study of the molecular forms of arylsulfatases confirmed the complete deficiency of arylsulfatase A and arylsulfatase B activities in metachromatic leukodystrophy and mucopolysaccharidosis type VI lymphoid cells, respectively [28].

Analytical, diagnostic and therapeutic context of Leukodystrophy, Metachromatic

• Arylsulfatase A polypeptides were examined in cultured fibroblasts from a patient with juvenile metachromatic leukodystrophy and three patients with the adult form of the disease, with the aid of metabolic labeling and immunoprecipitation [29].
• Auditory evoked brainstem response and high-performance liquid chromatography sulfatide assay as early indices of metachromatic leukodystrophy [30].
• Arylsulfatase A (ASA) knockout mice represent an animal model for the lysosomal storage disease metachromatic leukodystrophy (MLD) [31].
• 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) [32].
• HPLC analysis of urinary sulfatide: an aid in the diagnosis of metachromatic leukodystrophy [33].

References