Disease relevance of SGSH

• Mucopolysaccharidosis type IIIA (MPS IIIA) is an autosomal recessive disease that occurs due to a deficiency of heparan sulfate sulfamidase (SGSH) [1].
• Mucopolysaccharidosis type IIIA (MPSIIIA) is an autosomal recessive lysosomal storage disease caused by mutations in the N-sulfoglucosamine sulfohydrolase gene (SGSH; encoding sulfamidase, also sulphamidase) leading to the lysosomal accumulation and urinary excretion of heparan sulfate [2].
• Sanfilippo A syndrome (mucopolysaccharidosis type IIIA, MPS-IIIA) is an autosomal recessive neurodegenerative disorder due to an enzymatic defect of the lysosomal enzyme sulphamidase (EC 3.10.1.1) required for the degradation of heparan sulphate [3].
• Sulphamidase is one of four lysosomal proteins whose deficiency clinically manifests as Sanfilippo syndrome [4].
• Cell fusions were performed to investigate the possible involvement of different gene mutations in five patients with isolated beta-mannosidosis and a patient with a combined deficiency of beta-mannosidase and heparin sulphate sulphamidase [5].

Psychiatry related information on SGSH

• Some CIDI- SFMD positive subjects may have had depressive symptoms attributable to organic or other etiologies excluded under the definition of major depression [6].

High impact information on SGSH

• Recombinant human sulphamidase was able to correct the storage phenotype of MPS IIIA fibroblasts after endocytosis via the mannose-6-phosphate receptor [7].
• Recombinant human sulphamidase was purified from unamplified and amplified cell lines [7].
• To facilitate the development of enzyme-replacement strategies for MPS IIIA patients, we have constructed a high-level expression system for recombinant human sulphamidase in Chinese hamster ovary (CHO) cells [7].
• The deficiency of SGSH results in the lysosomal accumulation and urinary excretion of the glycosaminoglycan heparan sulfate [1].
• Heparan sulfate sulfamidase (HSS) is a lysosomal exohydrolase that, when deficient, results in intralysosomal accumulation of heparan sulfate and the clinical phenotype of Sanfilippo syndrome type A. The first animal disease homolog of human Sanfilippo syndrome type A has been recently indentified in Dachshund littermates [8].

Biological context of SGSH

• Most of the identified mutations in the SGSH and NAGLU genes are associated with severe clinical phenotypes [9].
• Early diagnosis of mucopolysaccharidosis III A with a nonsense mutation and two de novo missense mutations in SGSH gene [10].
• The coding region showed 87% nucleotide homology, and 89% amino acid sequence homology, with human HSS [8].
• To identify the molecular defect, the nucleotide sequences of the normal canine HSS gene and cDNA were determined using PCR-based approaches [8].
• Sulphamidase catalyses the hydrolysis of an N-linked sulphate from the nonreducing terminal glucosaminide residue of HS (Fig. 1). It is unique among the known lysosomal sulphatases involved in GAG degradation in that it is an N-sulphatase, all the others being O-sulphatases [4].

Anatomical context of SGSH

• Many of the missense, nonsense, and insertion/deletion mutations have been expressed in mammalian cell lines to permit the characterization of their effects on SGSH and NAGLU activity and intracellular processing and trafficking [9].
• Leukocytes from 21 obligate carriers in 12 Sanfilippo A families and 49 normal controls were assayed for heparan sulphamidase (EC 3.10.1.1) at 55 degrees C. At this assay temperature the results show an absolute distinction between heterozygous carriers and the normal controls [11].
• Previously, prenatal diagnosis of Sanfilippo A syndrome has been achieved by a radioactive sulphamidase assay in chorionic villi or in cultured amniocytes and by two-dimensional electrophoresis of glycosaminoglycans in amniotic fluid [12].
• We have investigated the use of a 4-methylumbelliferone (MU)-derived artificial substrate, MU-alpha-D-N-sulphoglucosaminide, for the sulphamidase assay in chorionic villi and amniotic fluid cells [12].
• CONCLUSION: In vitro, treatment of HSS cells with FGF-1 stimulates cell growth and induces expression of differentiation markers specific to osteoblasts [13].

Associations of SGSH with chemical compounds

• MPS-IIIA and MPS-IIIB involve deficiencies of heparan sulfate sulfamidase (SGSH) and alpha-N-acetylglucosaminidase (NAGLU), respectively [9].
• Sulphamidase activity in leucocytes, cultured skin fibroblasts and amniotic cells: diagnosis of the Sanfilippo A syndrome with the use of radiolabelled disaccharide substrate [14].
• Unequivocal assignment of the fetal status in five affected pregnancies and 17 pregnancies with a normal outcome confirms the reliability of the new sulphamidase assay, which is in every respect more convenient than the conventional method using 35S-radiolabelled heparin [12].
• To determine the sensitivity of HSS cells to ONOO- in the absence and presence of FGF-1 pretreatment, cells were exposed to varying concentrations of the oxidant and examined for cell death using quantitative fluorescence staining with fluorescein diacetate and propidium diacetate [13].

Analytical, diagnostic and therapeutic context of SGSH

• The entire coding region of the sulphamidase gene was RT-PCR amplified and one polymorphism (R456H), four novel mutations (S66W, R245H, E447K, 1307 del 9) and one previously described mutation (1284 del 11) were identified by direct PCR sequencing [3].
• The effect of FGF-1 on HSS cell expression of osteoblast-specific osteopontin and osteocalcin mRNA and protein was examined by reverse transcriptase polymerase chain reaction and Western blot techniques [13].
• To see if this was so, the authors examined a consecutive series of 235 posterior stabilized knee arthroplasties recording the results according to five rating systems: HSS (The Hospital for Special Surgery), Brigham, Freeman, BOA (British Orthopaedic Association), and the VENN diagram [15].
• The coated and the noncoated groups were matched for sex, age, body mass index, and HSS Knee Score [16].

References