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)

We report a new neurocutaneous syndrome of apparent autosomal recessive inheritance consisting of early-childhood-onset palmoplantar keratoderma followed in adulthood by progressive tetrapyramidal syndrome and cognitive impairment. Of the four affected siblings, two were available for evaluation. Investigation disclosed cerebral white-matter involvement on MRI and arylsulfatase A pseudodeficiency carrier state, which was also identified in clinically unaffected family members. Since skin biopsies showed dermal connective tissue abnormalities, we studied collagens I, III, and VI biosynthesis. Northern blotting of RNA extracted from cultured skin fibroblasts revealed an increased steady-state messenger RNA (mRNA) level of alpha 1(VI) collagen, whereas no differences were detected for pro alpha 1(I), pro alpha 1(III), and tropoelastin mRNAs. The skin content of collagen and total protein was higher in the patients than in controls. We suggest that an extracellular matrix abnormality may be involved in the pathogenesis of this disorder.
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PMID:Hereditary leukoencephalopathy and palmoplantar keratoderma: a new disorder with increased skin collagen content. 785 35

Metachromatic leukodystrophy is a rare autosomal recessive disorder with deficient arylsulphatase A activity. Different forms occur according to the age at onset of symptoms. Adult forms generally present with presenile dementia and/or psychiatric symptoms. We report a case of a 45-year-old woman, without a family history of neuropsychiatric disorders, presenting with complaints of numbness and weakness of the lower limbs. No intellectual or behavioral disturbances were clinically detectable. Electrophysiological investigation was compatible with severe demyelinating neuropathy in upper and lower limbs. MRI of the brain showed multiple white matter lesions. Adult metachromatic leukodystrophy was diagnosed on the basis of low leucocyte arylsulfatase-A-activity and accumulation of metachromatic material in the sural nerve. Pseudo-deficiency was excluded by DNA analysis. This case indicates that adult metachromatic leukodystrophy should be considered in patients with symptoms and signs resembling multiple sclerosis with peripheral neuropathy and in patients with neuropathy of unknown etiology.
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PMID:[Neuropathy in adult metachromatic leukodystrophy]. 801 55

We reported a family in which two brothers and one sister out of five siblings were affected by a neurological disease showing the following clinical manifestations: 1) intellectual disturbance with relative preservation of memory and orientation probably developed on child food, 2) spastic paraparesis beginning at the age of about 20 years, 3) mild peripheral neuropathy and cerebellar sign. Their clinical courses were stereotyped, and so much the worse in elder patients. Two of them were investigated in detail. Laboratory findings including chromosomal analysis, amino acid analysis and thyroid function were normal. HTLV-1 antibody was negative. Several lymphocytes lysosomal enzymes including beta-hexosaminidase and arylsulfatase A and serum very long fatty acids were also within normal range. CT and MRI showed characteristic thinning of corpus callosum, dominant in anterior portion. However, changes in intensity of white matter in T2 weighted image were not so prominent. In the older patient, more mentally deteriorated, were demonstrated hypoperfusion in the fronto-parietal lobes by SPECT and slow wave bursts dominant in the same region by EEG. Therefore, we considered that the change of corpus callosum was hypoplasia, but not atrophy, and it may provoke dysfunction of relevant nervous system. Family cases of such clinical feature were rare. We could confirm only three families in literatures, all of them were Japanese.
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PMID:[Familial cases of spastic paraparesis, mental disturbance and thinning of the corpus callosum]. 836 56

We treated a 28-year-old woman who had metachromatic leukodystrophy with bone marrow transplantation. Leukocyte arylsulfatase A levels increased to the donor's range after successful graft. Motor and sensory nerve conduction values did not change significantly in the 4 years after the transplant, and subcortical white matter lesions, as shown on MRI, remained stable during that period of time. The results, after 4 years of follow-up, indicate that the disease has not progressed and signs and symptoms are stabilized.
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PMID:Late juvenile metachromatic leukodystrophy treated with bone marrow transplantation; a 4-year follow-up study. 855 89

Delayed demyelination is a rare and poorly understood complication of hypoxic brain injury. A previous case report has suggested an association with mild-to-moderate deficiency of arylsulfatase A. We describe a 36-year-old man who recovered completely from an episode of hypoxia related to drug overdose, and 2 weeks later progressed from a confusional state to deep coma. MRI showed diffuse white matter signal changes, and brain biopsy demonstrated a noninflammatory demyelinating process. Proton magnetic resonance spectroscopy revealed elevated choline and lactate and reduced N-acetyl aspartate signal in the affected white matter, consistent with demyelination and a shift to anaerobic metabolism. Arylsulfatase A activity from peripheral leukocytes was approximately 50% of normal, consistent with a "pseudodeficiency" phenotype. These findings confirm the hypothesis that relative arylsulfatase A deficiency predisposes susceptible individuals to delayed posthypoxic leukoencephalopathy and implicates lactic acidosis in the pathogenesis of this disorder.
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PMID:Delayed posthypoxic demyelination. Association with arylsulfatase A deficiency and lactic acidosis on proton MR spectroscopy. 978 85

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

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder due to deficiency of the enzyme arylsulfatase A that leads to progressive, diffuse demyelination. The syndrome of nonverbal learning disability has been attributed to white matter abnormality and has been reported in children with this disorder and in some healthy family member carriers of gene. We examined the neuropsychologic profiles and MRIs of eight members of the family of a 7-year-old girl with this disease, all of whom were heterozygous carriers of the mutation and five of whom were also carriers of the MLD pseudodeficiency gene. All had low normal levels of arylsulfatase A, and seven of the eight had average or better profiles across all assessed neuropsychological domains. The patient's younger sister had a profile with features of the syndrome of nonverbal learning disability despite a normal MRI, whereas two members with minor white matter findings did not. This family does not provide evidence for the syndrome of nonverbal learning disability in heterozygous carriers of the gene for MLD, even when associated with the MLD pseudodeficiency gene.
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PMID:Metachromatic leukodystrophy and nonverbal learning disability: neuropsychological and neuroradiological findings in heterozygous carriers. 1181 81

In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N-acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and MPS VI patients often develop spinal cord compression during the course of the disease due to GAG storage within the cervical meninges, requiring neurosurgical intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not expected to cross the blood-brain barrier. We report the use of intrathecal (IT) recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in a MPS VI child with spinal cord compression whose parents initially refused the surgical treatment. Assessments were performed at baseline, with clinical, neurological and biochemical evaluations, urodynamic studies and MRI of the CNS. Changes on these parameters were evaluated after IT infusions of ASB administered monthly via lumbar puncture (LP) in a IV ERT naive patient. To our knowledge, this was the first MPS VI patient who received IT ERT. Despite significant urodynamic improvement and some neurological amelioration, the patient developed worsening of walking capacity. After IV ERT was started, the patient presented with a generalized hypotonia and a life-saving surgical fixation of the neck was then performed. The results observed on this MPS VI patient suggest that instability of the cervical vertebrae could be unmasked by IV ERT as joint storage is reduced, and the decrease in neck stiffness and stability could confound the expected improvement of SCC manifestations following IT ERT. The study of further patients, if possible in a clinical trial setting, is needed to evaluate the potential of a non-surgical IT ERT treatment of SCC for MPS VI.
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PMID:Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis. 2003 75

Spinocerebellar ataxia type15 (SCA15) is a pure ataxia characterized by very slow progression. Only seven families have been identified worldwide, in which partial deletions and a missense mutation of the inositol triphosphate receptor type I gene (ITPR1) have been reported. We examined a four-generation Italian family segregating an autosomal dominant cerebellar ataxia, in which linkage analysis was positive for the SCA15 locus. We performed a genomic real-time polymerase chain reaction to search for ITPR1 gene deletions in this family and in 60 SCA index cases negative for mutations in the SCA1-3, 6-8, 10, 12,and dentatorubral-pallidoluysian atrophy genes. The deleted segments were characterized using a custom array comparative genomic hybridization analysis. We have identified two families with an ITPR1 gene deletion: in one, the deletion involved ITPR1 only, while in the other both sulfatase-modifying factor 1 and ITPR1. Clinical data of ten patients and brain MRI (available for six) showed that the phenotype substantially overlapped known SCA15 cases,but we also noted buccolingual dyskinesias, facial myokymias,and pyramidal signs never reported in SCA15. ITPR1 expression analysis of two deleted cases showed a half dose. Our results further support ITPR1 gene as causative of SCA15. The families reported show that SCA15 is present in Italy and has a greater variability in the age at onset and clinical features than previously reported. We propose that the search for ITPR1 deletions is mandatory in the clinical hypothesis of SCA15 and that ITPR1-reduced expression in blood may be a useful marker to identify SCA15 patients harboring genomic deletions and possibly point mutations causing reduction of mRNA level.
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PMID:Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. 2008 66

We describe one patient and review the literature to define delayed posthypoxic leukoencephalopathy, its etiology, pathophysiology and prognosis. We present a 54-year-old man with confusion and diffuse rigidity following a morphine overdose that had required intubation three weeks previously. A brain CT scan showed bilateral globi pallidi hypodensities and diffusion-weighted brain MRI (DWI) was consistent with acute cerebral anoxia. On day 20 after the initial presentation, the patient insidiously progressed to a state of "akinetic mutism". The brain MRI showed diffuse hyperintensity of the white matter on T2-weighted fluid-attenuated inversion recovery sequences. These areas were bright on DWI and were hypointense on the apparent diffusion coefficient map. An extensive autoimmune, metabolic, toxicological, and infectious work-up included arylsulfatase A enzyme levels, which were unremarkable. Therapy with levodopa was initiated with subsequent improvement of the diffuse rigidity. At discharge, the patient continued to be lethargic with moderate rigidity but began to display signs of recovery. He eventually fully recovered with residual mild confusion. Thus, delayed hypoxic leukoencephalopathy is a rare complication of hypoxic-ischemic encephalopathy, occurring in 2.75% of victims of carbon monoxide poisoning. It typically manifests two to 40 days after apparent recovery from an obtunded state. Prognosis is variable, but recovery can be complete. This report brings to light an important syndrome that can easily be misdiagnosed. Patients who present with these clinical and radiographic features should be treated fully and given time to recover without abrupt withdrawal of care.
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PMID:Delayed posthypoxic leukoencephalopathy following a morphine overdose. 2255 27


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