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)

Multiple sulfatase deficiency is a rare autosomal recessive disorder in which affected individuals present a complex phenotype due to the impaired activity of all sulfatases. There are different types of multiple sulfatase deficiency; among them, the neonatal form is the most severe, with a broad range of mucopolysaccharidosis-like symptoms and death within the first year of life. The disorder is caused by homozygous or compound heterozygous mutations in the sulfatase-modifying factor-1 (SUMF1) gene. In this article, we describe a non-ichthyotic neonatal multiple sulfatase deficiency patient with a novel mutation in the SUMF1 gene. The missense mutation c.777C>G, for which the patient was homozygous, had been caused by a p.N259K amino acid substitution. We evaluated the patient using clinical findings, neuroimaging studies and molecular analysis via the literature; we also wanted to note the difficulties in the diagnosis of this rare disease.
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PMID:Neonatal multiple sulfatase deficiency with a novel mutation and review of the literature. 2581 62

Background Metachromatic leukodystrophy (MLD) is an autosomal recessively (AR) inherited disease caused by the deficiency of the enzyme arylsulfatase A (ARSA). Although MLD is the most common form of hereditary leukoencephalopathy, it is still very rare. More than 200 gene mutations have been identified in the ARSA gene. The most frequently identified mutation is the one located on chromosome 22q13.33. In the present study, new mutations are reported in two siblings of different ages and with different clinical presentations. Case presentation A 9-year-old male patient, suffering from ataxia, attention deficit and perceptual difficulties, was first seen at the age of 7. While the findings of neurological examination and neuroradiological evaluation suggested MLD, the ARSA enzyme levels were analyzed and found to be at a lower limit. Genetic analysis revealed variant homozygous mutations of the ARSA gene at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. In the genetic analysis of his three siblings and parents, a variant heterozygous mutation of the ARSA gene was detected at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. Conclusions MLD is a rare disease; however, it is likely to find different variant forms in our population, in which the frequency of consanguineous marriages is high. Genetic diagnosis is important in symptomatic cases with enzyme levels within the normal ranges.
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PMID:Two siblings with metachromatic leukodystrophy caused by a novel identified homozygous mutation in the ARSA gene. 3005 22

Mucopolysaccharidosis type IVA (MPS IVA) is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). We report here two GALNS pharmacological chaperones, ezetimibe and pranlukast, identified by molecular docking-based virtual screening. These compounds bound to the active cavity of GALNS and increased its thermal stability as well as the production of recombinant GALNS in bacteria, yeast, and HEK293 cells. MPS IVA fibroblasts treated with these chaperones exhibited increases in GALNS protein and enzyme activity and reduced the size of enlarged lysosomes. Abnormalities in autophagy markers p62 and LC3B-II were alleviated by ezetimibe and pranlukast. Combined treatment of recombinant GALNS with ezetimibe or pranlukast produced an additive effect. Altogether, the results demonstrate that ezetimibe and pranlukast can increase the yield of recombinant GALNS and be used as a monotherapy or combination therapy to improve the therapeutic efficacy of MPS IVA enzyme replacement therapy.
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PMID:Identification of Ezetimibe and Pranlukast as Pharmacological Chaperones for the Treatment of the Rare Disease Mucopolysaccharidosis Type IVA. 3118 88

Multiple sulfatase deficiency (MSD, MIM #272200) is an ultra-rare disease comprising pathophysiology and clinical features of mucopolysaccharidosis, sphingolipidosis and other sulfatase deficiencies. MSD is caused by impaired posttranslational activation of sulfatases through the formylglycine generating enzyme (FGE) encoded by the sulfatase modifying factor 1 (SUMF1) gene, which is mutated in MSD. FGE is a highly conserved, non-redundant ER protein that activates all cellular sulfatases by oxidizing a conserved cysteine in the active site of sulfatases that is necessary for full catalytic activity. SUMF1 mutations result in unstable, degradation-prone FGE that demonstrates reduced or absent catalytic activity, leading to decreased activity of all sulfatases. As the majority of sulfatases are localized to the lysosome, loss of sulfatase activity induces lysosomal storage of glycosaminoglycans and sulfatides and subsequent cellular pathology. MSD patients combine clinical features of all single sulfatase deficiencies in a systemic disease. Disease severity classifications distinguish cases based on age of onset and disease progression. A genotype- phenotype correlation has been proposed, biomarkers like excreted storage material and residual sulfatase activities do not correlate well with disease severity. The diagnosis of MSD is based on reduced sulfatase activities and detection of mutations in SUMF1. No therapy exists for MSD yet. This review summarizes the unique FGE/ sulfatase physiology, pathophysiology and clinical aspects in patients and their care and outlines future perspectives in MSD.
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PMID:Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification. 3241 21