Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Kresse, Hans; Paschke, Eduard; Figura, Kurt Von; Gilberg, W; Fuchs, W

doi:10.1073/pnas.77.11.6822

Cited by 103 publications

(59 citation statements)

References 32 publications

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“…Then 20 ml of water was added, and the solution was neutralized and applied to a 5 ml column of Dowex 1 (Cl-form), which was washed with 50 ml of water and then with 20 ml of 1 M-LiCl. The LiCl eluate was concentrated to 4 ml by rotary evaporation and desalted on a Sephadex G-10 column (100 cm x 1 cm diam.) developed in 10% (v/v) ethanol in water.…”

Section: Methodsmentioning

confidence: 99%

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Human liver N-acetylglucosamine-6-sulphate sulphatase. Purification and characterization

Freeman

Clements

Hopwood

1987

Biochemical Journal

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Human N-acetylglucosamine-6-sulphate sulphatase was purified at least 50000-fold to homogeneity in 780%yield from liver with a simple three-step four-column procedure, which consists of a concanavalin A-Sepharose/Blue A-agarose coupled step, chromatofocusing and Cu2+-chelating Sepharose chromatography. In all, four forms were isolated and partially characterized. Forms A and B, both with a pl greater than 9.5 and representing 30% and 60% respectively of the recovered enzyme activity, were separated by hydroxyapatite chromatography of the enzyme preparation obtained from the Cu2+-chelating Sepharose step. Both forms A and B had native molecular masses of 75 kDa. When analysed by SDS/polyacrylamide-gel electrophoresis, form A consists of a single polypeptide of molecular mass 78 kDa, whereas form B contained 48 kDa and 32 kDa polypeptide subunits. Neither form A nor form B was taken up from the culture medium into cultured human skin fibroblasts. The two other forms (C and D), with pI values of 5.8 and 5.4 respectively, represented approx. 7% and 3% of the total recovered enzyme activity. The native molecular masses of forms C and D were 94 kDa and approx. 75 kDa respectively. Form C contained three polypeptides with molecular masses of 48, 45 and 32 kDa. N-Acetylglucosamine-6-sulphate sulphatase activity was measured with a radiolabelled disaccharide substrate derived from heparin. The development of this substrate enabled the isolation and characterization of N-acetylglucosamine-6-sulphate sulphatase to proceed efficiently. Forms A, B and C had pH optima of 5.0, Km values of 11.7, 14.2 and 11.1 LM respectively and Vmax values of 105, 60 and 53 nmol/min per mg of protein respectively. The molecular basis of the multiple forms of this sulphatase is not known. It is postulated that the differences in structure and properties of the four enzyme forms are due to differences in the state of processing of a large subunit.

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Section: Methodsmentioning

confidence: 99%

“…The de-O-sulphation of nonreducing terminal N-acetylglucosamine 6-sulphate (GlcNAc6S) residues in heparan sulphate requires a specific exo-sulphatase, namely N-acetylglucosamine-6-sulphate sulphatase (6SS), which has been shown to be deficient in Sanfilippo D (MPS IIID) patients [4].…”

Section: Introductionmentioning

confidence: 99%

Human liver N-acetylglucosamine-6-sulphate sulphatase. Purification and characterization

Freeman

Clements

Hopwood

1987

Biochemical Journal

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“…Sanfilippo syndrome type D (Mucopolysaccharidosis type IIID, MPS IIID) was first reported in 1980 by Kresse et al in a patient from East India (Kresse et al, 1980). Since then, only 19 MPS IIID patients have been reported (Beesley et al, 2003;Beesley et al, 2007;Coppa et al, 1983;del Canho H. et al, 1993;Gatti et al, 1982;Jansen et al, 2007;Jones et al, 1997;Kaplan and Wolfe, 1987;Ozand et al, 1994;Siciliano et al, 1991;TylkiSzymanska et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…GNS specifically cleaves a sulphate, bound at the 6-hydroxyl position moiety of N-acetylglucosamine from heparan and keratan sulphate (Kresse et al, 1980). However, keratan sulphate does not accumulate in MPS IIID, as the β-linked N-acetylglucosamine 6-sulphate can be cleaved off by β-hexosaminidase A (Kaplan and Wolfe, 1987;Kresse et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

et al. 2010

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Mucopolysaccharidosis III D (Sanfilippo disease type D, MPS IIID) is a rare autosomal recessive lysosomal storage disorder previously described in only 20 patients. MPS IIID is caused by a deficiency of N-acetylglucosamine-6-sulphate sulphatase (GNS), one of the enzymes required for the degradation of heparan sulphate. So far only seven mutations in the GNS gene have been reported. The clinical phenotype of 12 new MPS IIID patients from 10 families was studied. Mutation analysis of GNS was performed in 16 patients (14 index cases). Clinical signs and symptoms of the MPS IIID patients appeared to be similar to previously described patients with MPS III. Early development was normal with onset of behavioral problems around the age of 4 years, followed by developmental stagnation, deterioration of verbal communication and subsequent deterioration of motor functions. Sequence analysis of the coding regions of the gene encoding GNS (GNS) resulted in the identification of 15 novel mutations: 3 missense mutations, 1 nonsense mutation, 4 splice site mutations, 3 frame shift mutations, 3 large deletions and 1 inframe small deletion. They include the first missense mutations and a relatively high proportion of large rearrangements, which warrants the inclusion of quantitative techniques in routine mutation screening of the GNS gene.

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“…We observed recently that N-acetylglucosamine 6-sulphate residues of keratan sulphate-derived oligosaccharides may be removed in vitro as sulphated monosaccharides by fl-N-acetylhexosaminidase A , thus bypassing the action of an N-acetylglucosamine 6-sulphate sulphatase (Basner et al, 1979 . O (Kresse et al, 1980) and other materials (Ludolph et al, 1981) were obtained as described.…”

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confidence: 99%

Impaired degradation of keratan sulphate by Morquio A fibroblasts

Glössl¹,

Kresse²

1982

Biochemical Journal

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Upon incubation of keratan [35S]sulphate with normal fibroblasts both [35S]sulphate and N-acetylglucosamine 6-[35S]sulphate are liberated. From the products obtained after digestion with various mutant fibroblasts and with purified N-acetylgalactosamine 6-sulphate sulphatase we suggest that (i) [35S]sulphate is released almost exclusively from galactose 6-sulphate residues; (ii) N-acetylgalactosamine 6-sulphate sulphatase exhibits galactose 6-sulphate sulphatase activity; (iii) both sulphatase activities are deficient in Morquio disease type A.

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Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Cited by 103 publications

References 32 publications

Human liver N-acetylglucosamine-6-sulphate sulphatase. Purification and characterization

Human liver N-acetylglucosamine-6-sulphate sulphatase. Purification and characterization

Mucopolysaccharidosis type IIID: 12 new patients and 15 novel mutations

Impaired degradation of keratan sulphate by Morquio A fibroblasts

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