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

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (EC 3.1.6.1). This results in the intralysosomal storage of cerebroside sulphate, which leads to a progressive demyelination of the nervous system. The patients usually die within a few years from the onset of symptoms. Clinically, there are different forms of the disease and the molecular basis for this heterogeneity is unknown. The gene for arylsulphatase A has recently been cloned and provides a necessary tool for the exact description of the molecular defects occurring in the different forms of metachromatic leukodystrophy. Metachromatic leukodystrophy can also be caused by the deficiency of an arylsulphatase A activator protein (sphingolipid activator protein B). The cDNA for the precursor of this protein has been isolated and a mutant cDNA of one patient has been analysed. A substantial arylsulphatase A deficiency can also occur in healthy individuals, a phenotype termed pseudodeficiency. Two concurrent mutations have been identified in this low arylsulphatase A activity allele. This permitted the development of a rapid assay which allows the detection of the pseudodeficiency allele. Bone marrow transplantation has been tried in several metachromatic leukodystrophy patients and there is evidence that this treatment might slow or even halt the progression of the disease. A final conclusion as to whether bone marrow transplantation is a suitable therapy for metachromatic leukodystrophy cannot be drawn yet.
 ...
PMID:Advances in the molecular genetics of metachromatic leukodystrophy. 197 56

Mutated PSAP gene resulting in sphingolipid activator protein B deficiency is known to cause metachromatic leukodystrophy variant in which arylsulfatase A is normal. Of 16 patients with metachromatic leukodystrophy that were evaluated in our center, 7 patients were diagnosed with arylsulfatase A-deficient metachromatic leukodystrophy, whereas 9 children from 4 unrelated Saudi families were found to have sphingolipid activator protein B deficiency. PSAP analysis found that the 4 families segregate the same homozygous mutation that was a g.722G>C transversion resulting in C241S change, which was previously reported in an Arab patient. Our work, which reports the largest series of patients with sphingolipid activator protein B deficiency, suggests that this variant is likely to be more common than arylsulfatase A-deficient metachromatic leukodystrophy in Arabs, a notion that has potential diagnostic and preventive implications.
 ...
PMID:Sphingolipid activator protein B deficiency: report of 9 Saudi patients and review of the literature. 1995 43

Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively. The severity of clinical course in metachromatic leukodystrophy is determined by the residual ARSA activity, depending on the type of mutation. Currently, there is no effective treatment for this disease. Clinical cases of bone marrow or cord blood transplantation have been reported, however the therapeutic effectiveness of these methods remains insufficient to prevent aggravation of neurological disorders. Encouraging results have been obtained using gene therapy for delivering the wild-type ARSA gene using vectors based on various serotypes of adeno-associated viruses, as well as using mesenchymal stem cells and combined gene-cell therapy. This review discusses therapeutic strategies for the treatment of metachromatic leukodystrophy, as well as diagnostic methods and modeling of this pathology in animals to evaluate the effectiveness of new therapies.
 ...
PMID:Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches. 3319 24