Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblasts of four patients affected with mucosulfatidosis (multiple sulfatase deficiency, Austin variant of metachromatic leukodystrophy) were assayed for activities of the five sulfatases known to degrade mucopolysaccharides. These were iduronide 2-sulfate sulfatase, sulfamidase, N-acetyl-galactosamine 6-sulfate sulfatase, arylsulfatase B (N-acetylgalactosamine 4-sulfate sulfatase), and N-acetylglucosamine 6-sulfate sulfatase. The activities of these five sulfatases were severely depressed, thus confirming the known deficiency of arylsulfatase B and the absence of the Hunter and Sanfilippo III A corrective factors that have iduronide 2-sulfate sulfatase and sulfamidase activity, respectively. Together with earlier reports of the deficiencies of arylsulfatases A and C, cholesteryl sulfatase, and dehydroepiandrosterone sulfatae, mucosulfatidosis is now characterized by the deficiency of nine different sulfatases.
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PMID:Multiple deficiency of mucopolysaccharide sulfatases in mucosulfatidosis. 52 91

In an effort to improve the precision in prenatal monitoring for metachromatic leukodystrophy, levels of cerebroside sulfatase were determined in fibroblasts and amniotic fluid cells. Cells from MLD patients demonstrated no significant sulfatide hydrolysis, whereas cultures from heterozygous subjects hydrolyzed diminished but definite amounts of sulfatide. Cells from a fetus with low arylsulfatase A activity were able to cleave considerable amounts of sulfatide; enzyme assays performed postnatally suggest that the infant is heterozygous for MLD. This report documents the value of cerebroside sulfatase assays in the in utero monitoring for MLD.
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PMID:Cerebroside sulfatase activity in cultivated human skin fibroblasts and amniotic fluid cells;. 112 3

In a family with juvenile metachromatic leukodystrophy (sulfatide lipidosis) 2 patients showed residual arysulfatase A activities of 5--6%. The patients' healthy father was characterized biochemically by a 39% normal activity of leukocyte plus plasma arylsulfatase A. The father was further characterized by a high sulfatide excretion (0.2--0.5 mg/I urine) and, paradoxically, by a normal sulfatide degrading enzyme activity in vitro. This special carrier is suspected to be heterozygous for a) arylsulfatase A deficiency and b) arylsulfatase A (sulfatidase) lability. This presumed additional genetic defect could be the cause of the sulfatide excretion which, in turn, would be a sign of the preclinical stage of an exceptional form of adult metachromatic leukodystrophy. The normal sulfatidase activity seems to be due to an in vitro effect.
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PMID:Sulfatide excreting heterozygous carrier of juvenile metachromatic leukodystrophy or asymptomatic patient of adult metachromatic leukodystrophy. 117 45

The lysosomal removal of the sulfate moiety from sulfatide requires the action of two proteins, arylsulfatase A and sphingolipid activator protein-1 (SAP-1). Recently, patients have been identified who have a variant form of metachromatic leukodystrophy which is characterized by mutations in the gene coding for SAP-1, which is also called "prosaposin." All of the mutations characterized in these patients result in (a) deficient mature SAP-1, as determined by immunoblotting after SDS-PAGE of tissue and cell extracts, and (b) decreased ability of cultured skin fibroblasts to metabolize endocytosed [14C]-sulfatide. We now report the insertion of the full-length prosaposin cDNA into the Moloney murine leukemia virus-derived retroviral vector, pLJ, and the infection of cultured skin fibroblasts from a newly diagnosed and molecularly characterized patient with SAP-1 deficiency. The cultured cells infected with the prosaposin cDNA construct now show both production of normal levels of mature SAP-1 and completely normal metabolism of endocytosed [14C]-sulfatide. These studies demonstrate that the virally transferred prosaposin cDNA is processed normally and is localized within lysosomes, where it is needed for interaction between sulfatide and arylsulfatase A. In addition, normal as well as mutant sequences can now be found by allele-specific oligonucleotide hybridization of PCR-amplified genomic DNA by using exonic sequences as primers.
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PMID:Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured cells from a patient with SAP-1 deficiency. 135 Aug 85

We report on a new allele at the arylsulfatase A (ARSA) locus causing late-onset metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is highly conserved in the arylsulfatase gene family, is replaced by glutamine. In contrast to alleles that cause early-onset MLD, the arginine84 to glutamine substitution is associated with some residual ARSA activity. A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD.
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PMID:Late-onset metachromatic leukodystrophy: molecular pathology in two siblings. 135 40

Metachromatic leukodystrophy (MLD) is a neurologically devastating autosomal recessive disorder in humans associated with deficient arylsulfatase A activity. However, clinically normal individuals described as being pseudo-arylsulfatase-A deficient also demonstrate the same deficiency. Genotypically, they may be homozygous for the pseudodeficiency mutation (associated with 2 A-->G transitions in the cDNA of arylsulfatase A) or heterozygous with one pseudodeficiency and one MLD allele. Using as examples 2 families in which the pseudo deficiency condition occurs either independently or together with MLD, we demonstrate the utility of a proposed diagnostic protocol to provide complete genotype identification of individuals suffering from arylsulfatase A deficiency. Patient fibroblasts are extracted for DNA and a cytoplasmic fraction, which is used for arylsulfatase A enzyme assay. This will identify an arylsulfatase A-deficient group, which is further analyzed electrophoretically. Cells from the clinically affected patients with MLD are completely deficient in arylsulfatase A activity, whereas those from the pseudodeficient individuals demonstrate a characteristic residual arylsulfatase A activity detectable only after electrophoresis. Within this pseudodeficient group, gene amplification of DNA specific for the A-->G mutations will distinguish between those who are homozygous for the pseudodeficiency allele and those who are compound heterozygous for the pseudodeficiency and MLD alleles. This protocol of complete genotype identification requires only about 10(6) fibroblasts (1 x 100 mm dish) and 2 days to complete. Such variant-specific genotype identification increases accuracy and prognostic value of the diagnosis. It will likely become the preferred choice for diagnosis of genetic disease in the future as more variant-specific mutations are identified at the molecular level.
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PMID:Diagnosis of arylsulfatase A deficiency. 135 70

Sulfatide excretion in urine and arylsulfatase A (ASA) activity in leukocytes were determined in 10 homozygotes of metachromatic leukodystrophy (MLD), 7 obligate and 5 facultative MLD heterozygotes, 6 low ASA subjects (not related to MLD homozygotes), and in 9 controls. As compared to controls (sulfatides: 0-2 nmol/mg lipid; ASA: 101-287 nmol p-nitrocatechol/mg protein/hr), MLD homozygotes displayed highly increased sulfatide excretions (27-280 nmol) and low residual ASA activities (0-13 nmol). Of 12 MLD heterozygotes (ASA: 18-87 nmol) 10 showed increased sulfatides (3-24 nmol). All heterozygotes with ASA activity < 60 nmol (n = 8) had elevated sulfatide excretions (4-24 nmol). Thus, reduction of ASA activity below 40% of the mean value of controls seems to be the critical threshold for elevated sulfatide excretion in MLD heterozygotes. The low ASA subjects (ASA in the heterozygote range) excreted sulfatides in the control range, even those with ASA activities < 60 nmoles (n = 3; including a definite homozygote for ASA-pseudodeficiency; ASA:25 nmol). Statistical evaluation of sulfatide excretion and ASA activity in all subjects (n = 37) revealed a significant inverse relation (Spearman rank correlation; R = 0.8278, P < 0.001). The finding of elevated sulfatide excretion in certain MLD heterozygotes might point to increase of sulfatides also in the nervous system.
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PMID:Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy: dependence on reduction of arylsulfatase A activity. 135 86

Hereditary metabolic diseases are an exceptional cause of neurological disorders in adults. Metachromatic leukodystrophy is a hereditary alteration of the metabolism of myelin which may be manifested in adults as intellectual deterioration. A case of metachromatic leukodystrophy presented in adulthood is presented with cognitive deterioration and behavioral alterations as the only clinical manifestation. The patient was a 28 year old male studied for dementia of one year of evolution. Computerized tomography and cranial magnetic resonance demonstrated diffuse and symmetric involvement of the periventricular white matter. The visual evoked potentials were involved while the brain stem auditory potentials were normal. Study of the speed of nerve conductions was compatible with demyelinating neuropathy. The diagnosis of metachromatic leukodystrophy was confirmed by enzyme study revealing very diminished levels of aryl-sulfatase A. Although it is exceptional the adult form of metachromatic leukodystrophy should be included in the differential diagnosis of dementia. Computerized tomography and cranial magnetic resonance together with neurophysiologic studies are the principle procedures orienting diagnosis to this disease.
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PMID:[Metachromatic leukodystrophy: an exceptional cause of dementia in the adult]. 138 90

We describe eight patients with multiple sulfatase deficiency (MSD, or Austin's disease) who differ phenotypically from classic neonatal-, childhood-, or juvenile-onset MSD. The age of onset was in childhood. The patients presented with somatic and facial features of mucopolysaccharidosis reminiscent of Maroteaux-Lamy and Morquio syndromes. They differed from classic MSD by the presence of corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus and the absence of ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia. The main neurologic presentation was cervical cord compression due to axis abnormalities. Despite neuroradiologic evidence of white-matter changes, neurologic presentation was not like metachromatic leukodystrophy. The sulfatase deficiencies were more marked than in the classic juvenile form of MSD, but less marked than in the classic childhood-onset form of MSD. Steroid sulfatase activity was spared except in one patient. This Saudi variant of MSD accounts for 5% of all lysosomal storage diseases in the Cell Repository Registry of our Inborn Errors of Metabolism Laboratory.
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PMID:Saudi variant of multiple sulfatase deficiency. 158 9

The autopsy of a 2-year-old girl revealed a clinically unrecognized metachromatic leukodystrophy (MLD) due to an aryl-sulfatase A deficiency, characteristically affecting the central and peripheral nervous system by demyelination and by accumulation of metachromatic material. The retina though reported clinically as normal, showed the same demyelinating process in the optic nerve including the papilla but an additional intraneuronal storage of MLD-typical lysosomal residual bodies in ganglion cell perikarya of the retina. Cells of the bipolar and photoreceptor layers as well as pigment epithelial cells were not affected by MLD-specific lysosomal storage. Thus, sulfatides seem to play a particular metabolic role in ganglion cells but not in other neuronal cells of the retina in MLD.
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PMID:Ultrastructural study of the retina in late infantile metachromatic leukodystrophy. 160 95


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