The Defect in the Hunter Syndrome: Deficiency of Sulfoiduronate Sulfatase

Bach, Gideon; Eisenberg, Frank; Cantz, Michael; Neufeld, Elizabeth F.

doi:10.1073/pnas.70.7.2134

Cited by 210 publications

(81 citation statements)

References 23 publications

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“…The total sulfate content also decreased in the DS of this patient. These results are compatible with the finding by Bach et al (1973) that the proportion of unsaturated, disulfated disaccharides produced from GAG of Hunter fibroblasts by Chase ABC was reduced by one-third after treatment with the Hunter corrective factor (iduronosulfatase). These results suggest that iduronosulfatase releases sulfate groups linked not only to nonreducing terminal IdUA but also to some internal IdUA residues.…”

Section: Table 1 Analysis and Identification Of Fractionated Gagssupporting

confidence: 92%

Characteristics of urinay glycosaminoglycans excreted by a patient with the Hurler-Scheie compound syndrome.

Kimura

Hayashi

Koseki

et al. 1982

Tohoku J. Exp. Med.

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A., HAYASHI, S., KosEKI, M. and TSURUMI, K. Characteristics of Urinary G lycosaminoglycans Excreted by a Patient with the Hurler-Scheie Compound Syndrome. Tohoku J. exp. Med., 1982, 136 (1), [61][62][63][64][65][66] Glycosaminoglycan isolated from urine of a patient with the Hurler-Scheie compound syndrome consisted of dermatan sulfate (60°o)' heparan sulfate (34%) and chondroitin sulfate (6%). About 60% of both dermatan and chondroitin sulfates had molecular weight 8,000-10,000, while 95% of the heparan sulfate had molecular weight less than 6,000. The total sulfate content of the glycosaminoglycans increased with decrease in molecular weight. N-sulfate content in the heparan sulfate, however, had no relation to molecular weight, and was 0.33 mole per mole of glucosamine on the average. About 70% of the heparan sulfate with the lowest molecular weight (1,500) were composed of three repeating disaccharide units of heparan sulfate and two acetyl, one N-sulfate and three 0-sulfate groups linked to the units. The dermatan sulfate contained 1.0-1.2 moles of sulfate per mole of galactosamine. Of the excess sulfate 45-65% were bound to iduronate residues and the rest to C-6 of N-acetylgalactosamine 4-sulfate residues. Most of the dermatan sulfate (83.2-100%) had nonsulfated iduronic acid at the non-reducing end. This finding is consistent with the defect of iduronidase in this disease. ---mucopolysaccharidosis; Hurler-Scheie compound syndrome; urinary glycosaminoglycan; heparan sulfate; dermatan sulfateThe mucopolysaccharidoses, including the Hurler-Scheie compound syndrome, are caused by the deficiency of specific enzymes for glycosaminoglycan (GAG) degradation, and characterized by the excessive accumulation and abnormal excretion of GAGS. To learn the effect of the enzyme deficiency on the structure of the abnormally excreted GAGS, we attempted to isolate and characterize the urinary GAGS in various types of the mucopolysaccharidosis.Our previous studies on the urinary GAGS from a patient with the Hunter syndrome (iduronosulfatase deficiency) showed that the dermatan sulfate (DS) and the heparan sulfate (HS) was heterogeneous in molecular weight and sulfate content, and that the DS had an iduronosulfate residue at the non-reducing end, consistent with the defect of iduronosulfatase in that disease (Kimura et al. 1980a, b).In the present paper we demonstrate the structural features of urinary GAG

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Section: Table 1 Analysis and Identification Of Fractionated Gagssupporting

confidence: 92%

Characteristics of urinay glycosaminoglycans excreted by a patient with the Hurler-Scheie compound syndrome.

Kimura

Hayashi

Koseki

et al. 1982

Tohoku J. Exp. Med.

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“…1), which was consistent with the removal of sulfate from the terminal nonreducing iduronic acid of partially degraded dermatan and heparan sulfates by idurono-sulfate sulfatase (32)(33)(34). The action of idurono-sulfate sulfatase would then enable free iduronic acid to be released.…”

Section: +19supporting

confidence: 66%

Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome.

Dean¹,

Stevens²,

Muir³

et al. 1979

J. Clin. Invest.

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A B S T R A C T We have assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunter's syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of a-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that we were able to assess. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.

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“…Thus, following these different and complementary approaches, the enzyme deficiencies responsible for the impaired degradation of dennatan sulfate andlor heparan sulfate (DS, HS) which occurs in HurlerIScheie (3.27.40). Hunter (2,36), Sanfilippo A (20) and Bglucuronidase deficiency (17) diseases were identified. Subsequently, the enzyme deficiencies occurring in Sanfilippo B (29) and Maroteaux-Lamy (37) diseases have also been identified.…”

Section: Methodsmentioning

confidence: 99%

N-Acetylglucosamine-6-Sulfate Sulfatase in Man: Deficiency of the Enzyme in a New Mucopolysaccharidosis

et al. 1978

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SummaryThe study of a I y e a r old patient with a mucopolysaccharidosis different from those already known has given the opportunity to describe the clinical, biochemical and enzymic characteristics of N-acetylglucosamine-6-sulfate sulfatase deficiency.The patient was delayed physically and mentally, was hyperactive, and had a short attention span. He had fair complexion and verv blond. but coarse and excessive hair. He had mild hepatosplknomegaly and dysostosis multiplex, including hypoplastic odontoid Drocess of the atlas. ovoid vertebral bodies, small femoral epiphyses; and modest enlaigement of the ribs. He had. a mild, bilateral conductive hearing loss. The urine gave a strongly positive spot test with Azur A paper. Quantitative measurement of urinary glycosaminoglycans demonstrated increased excretion and inadequate degradation of heparan sulfate and keratan sulfate. The microscopic examination of the stained peripheral leukocytes revealed metachromatic material which formed a ring on the inner aspect of the cellular membrane in 20% of the lymphocytes. The rate of degradation of 35S04-labeled intracellular glycosaminoglycans by cutaneous fibroblasts was delayed and inadequate.The measurements of several lysosomal enzymes whose deficiencies are responsible for the known mucopolysaccharidoses gave results within normal ranges. Galactose-6-sulfate (Gal&S), N-acetylgalactosamine-6-sulfate (GalNAc-6-S), and N-acetylglucosamine-6-sulfate (GlcNAc-6-S) were prepared with chlorosulfonic acid, according to the method of Suzuki and Strominger (38). After chromatographic purification, aliquots of the three 6-sulfated monosaccharides were reduced with sodium borotritide.

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The Defect in the Hunter Syndrome: Deficiency of Sulfoiduronate Sulfatase

Cited by 210 publications

References 23 publications

Characteristics of urinay glycosaminoglycans excreted by a patient with the Hurler-Scheie compound syndrome.

Characteristics of urinay glycosaminoglycans excreted by a patient with the Hurler-Scheie compound syndrome.

Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome.

N-Acetylglucosamine-6-Sulfate Sulfatase in Man: Deficiency of the Enzyme in a New Mucopolysaccharidosis

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