Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The Sanifilippo syndrome is an inherited dementia caused by defective degradation of heparan sulfate. In the course of its catabolism the heparan sulfate polymer must be desulfated. Heparan sulfate sulfatase activity was demonstrated in homogenates of normal tissues and cultured skin fibroblasts, and in normal urine. This activity was found to be grossly depressed or absent in necropsy specimens of liver and spleen from two Sanfilippo patients. The heparan sulfate sulfatase activity was not demonstrable in urine from eleven, or cultured fibroblasts from four Sanfilippo patients. Activities of alpha-N-acetyl-glucosaminidase, the site of the metabolic defect in the Sanfilippo B variant were either normal or slightly elevated in the Sanfilippo tissues and cultured fibroblasts whereas the mean level in the urine of our Sanfilippo patients was about one-third of that encountered in control urines.
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PMID:Defective heparan sulfate metabolism in the Sanfilippo syndrome and assay of this defect in the assessment of the mucopolysaccharidoses patient. 23 59

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

A 20-year-old female had psychiatric symptoms of organic brain disease for five years but without clinical or neurophysiological signs of polyneuropathy. Late-onset metachromatic leukodystrophy was confirmed by finding severely reduced arylsulfatase A activity in her urine and leukocytes, marked excretion of sulfatides in the urine and the presence of lysosomal residual bodies in a sural nerve biopsy. This case report emphasizes the need to screen patients with early onset dementia of unknown origin or atypical hebephrenia, who are often confined to mental institutions early in the course of their disease.
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PMID:Late-onset metachromatic leukodystrophy: diagnostic problems elucidated by a case report. 618 81

Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of sulfamidase. The resulting lysosomal storage of heparan sulfate may lead to severe neurodegeneration preceded by progressive dementia, often combined with aggressive and hyperactive behaviour. A total of 109 patients from four different geographic areas were screened for the common mutation R245H and two other previously identified mutations. SSCP analysis of exons was used to characterize the unknown alleles. We identified 16 novel sequence variants, 12 of them likely to be pathogenic. The majority of the pathogenic variants were single base pair changes leading to missense mutations. Several single base pair deletions/insertions and one nonsense mutation were also identified. Altogether, we were able to characterize 55% of the pathogenic alleles. Sequence homology between sulfamidase and N-acetylgalactosamine 4-sulfatase, the first sulfatase to have its tertiary structure defined, suggests that amino acid residues R74 and T79, which were found to be mutated, are likely to be involved in the formation of the active site of sulfamidase. R245H accounts for 31% of the Sanfilippo A alleles in Australasia, for 19.2% of the alleles in patients from the UK and has a high frequency of 57.8% in patients from The Netherlands. The identification of mutations common in certain geographic regions or ethnic groups will help in the diagnosis of MPS IIIA and allow carrier testing and improved genetic counselling.
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PMID:Novel mutations in Sanfilippo A syndrome: implications for enzyme function. 928 96

We report here a familial observation of metachromatic leukodystrophy (MLD) in 2 sisters. The very beginning, with only psychiatric manifestations at adolescence, could be precisely established. The evolution towards a dementia, and the evidence of a pyramidal syndrome oriented later towards a clearly organic disease. A very wide bilateral and symmetrical demyelination was shown by Magnetic Resonance imaging. The deficiency in arylsulfatase A activity oriented towards MLD which was confirmed by metachromatic deposits in the nerve biopsy. Molecular biology evidenced in the two, compound heterozygoty with both the classical mutation of the infantile form with loss of a splicing site at the level of intron 2, and the ileu > Ser 179 mutation frequent in adult forms.
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PMID:[2 familial cases of metachromatic leukodystrophy of late onset]. 929 33

We reported two siblings with adult-type metachromatic leukodystrophy (MLD). Patient 1 was a 19-year-old male, and patient 2 was a 20-year-old female. Their initial symptoms were similar. They developed abnormal behavior and personality changes, poor concentration, and inappropriate smiling. In patient 1, his condition deteriorated and he developed incontinence. His attention span and verbal expression severely decreased. He had an inability to engage in meaningful conversation. The siblings were diagnosed as having MLD by marked reduced leukocyte arylsulfatase A activity. T2-weighted MRI of these two cases showed a high intensity area in the cerebral white matter. The high intensity areas of the cerebral white matter gradually spread over one year. However, SPECT of these cases showed only a few abnormal findings in the initial stage. Using SPECT, a reduction of regional cerebral blood flow (rCBF) spreading to the cerebral cortex was seen over one year after it was seen using MRI. The discrepancy between MRI and SPECT findings in the initial stage was characteristic. MLD is an important disease that involves white matter dementia. The discrepancy between MRI and SPECT is helpful to diagnose white matter dementia.
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PMID:[Two siblings with adult-type metachromatic leukodystrophy: correlation between clinical symptoms and neuroimaging]. 1089 6

An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and attention deficits with a slow psychomotor speed. MR brain imaging displayed confluent hyperintensities of periventricular and subcortical white matter. Low levels of arylsulfatase A confirmed the diagnosis. Impaired cortical glucose metabolism especially of the medial temporal and frontal cortices was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism.
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PMID:Dementia with impaired temporal glucose metabolism in late-onset metachromatic leukodystrophy. 1117 79

Mucopolysaccharidosis type IIID (MPS IIID) is a lysosomal storage disorder resulting from lack of activity of the lysosomal hydrolase N-acetylglucosamine 6-sulfatase (6S) (EC 3.1.6.14). The syndrome is associated with systemic and central nervous system (CNS) heparan sulfate glycosaminoglycan (HS-GAG) accumulation, secondary storage of lipids, and severe, progressive dementia. In this investigation, caprine MPS IIID, established as a large animal model for the human disease, was used to evaluate the efficacy of enzyme replacement therapy (ERT). Recombinant caprine 6S (rc6S) (1 mg/kg/dose) was administered intravenously to one MPS IIID goat kid at 2, 3, and 4 wks of age. Five days after the last dose, the uronic acid (UA) content and the composition of uncatabolized HS-GAG fractions in the brain of the ERT-treated MPS IIID kid were similar to those from a control, untreated MPS IIID animal. However, hepatic uronic acid levels in the treated MPS IIID kid were approximately 90% lower than those in the untreated MPS IIID control; whereas the composition of the residual hepatic HS-GAG was identical to that in the untreated animal. Marked reduction of lysosomal storage vacuoles in hepatic cells of the treated MPS IIID kid was observed, but ERT had no effect on CNS lesions. No residual 6S activity was detected in brain or liver. This preliminary investigation indicates that other treatment regimens will be necessary to ameliorate MPS III-related CNS lesions.
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PMID:Caprine mucopolysaccharidosis IIID: a preliminary trial of enzyme replacement therapy. 1130 88

A 29-year-old female patient with juvenile metachromatic leukodystrophy diagnosed at age 14 years received a bone marrow transplant at age 16 years. A report was published 6 years after bone marrow transplantation concluding that the disease had slowly progressed in the 2 years following bone marrow transplantation. We now report on a further 7-year follow-up, typified by a steady state of spastic paraplegia and mild dementia. Neurophysiological, neuroradiological, and psychological status also remained stable. In the patient's leukocytes, the activity of arylsulfatase A, the enzyme deficient in untreated metachromatic leukodystrophy, was within the normal range whereas urinary sulfatides remained elevated. 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. The long-term stabilization in this patient, however, suggested that bone marrow transplantation may halt the progression of juvenile metachromatic leukodystrophy.
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PMID:Stabilization of juvenile metachromatic leukodystrophy after bone marrow transplantation: a 13-year follow-up. 1789 Apr 17


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