Sanfilippo A syndrome. Sulfamidase deficiency in cultured skin fibroblasts and liver

Reuben Matalon, A. Dorfman

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The Sanfilippo A syndrome is an autosomal recessive mucopolysaccharidosis characterized clinically by severe mental retardation and biochemically by storage in tissue and excretion in urine of excessive amounts of heparan sulfate. Since sulfamide groups are present in heparan sulfate, a sulfamidase deficiency could explain the impaired degradation of this polysaccharide. To investigate the enzymic basis of this disease, assays for sulfamidase were performed. Extracts of cultured fibroblasts and post mortem liver were prepared by suspension of tissues in acetate: NaCl buffer, pH 4.5, containing Triton X 100 (Rohm and Haas Co., Philadelphia, Pa.), sonication, and centrifugation at 10,000 g. The supernatant fluid was incubated with [35S] N sulfated heparin. The release of inorganic sulfate after 18 hr of incubation was determined by chromatography on Sephadex G 25. The liver and fibroblast extracts of patients with the Sanfilippo A syndrome showed a deficiency of sulfamidase. The quantity of heparan sulfate in fibroblasts derived from patients with Sanfilippo A, Hurler's and Hunter's diseases was found to be 7-10%, while it was about 1.25% of the total glycosaminoglycans in fibroblasts of normal controls.

Original languageEnglish (US)
Pages (from-to)907-912
Number of pages6
JournalJournal of Clinical Investigation
Volume54
Issue number4
StatePublished - 1974
Externally publishedYes

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Mucopolysaccharidosis III
Heparitin Sulfate
Fibroblasts
Skin
Liver
Mucopolysaccharidoses
Mucopolysaccharidosis I
Liver Extracts
Sonication
Octoxynol
Glycosaminoglycans
Centrifugation
Intellectual Disability
Sulfates
Polysaccharides
Heparin
Chromatography
Suspensions
Buffers
Acetates

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sanfilippo A syndrome. Sulfamidase deficiency in cultured skin fibroblasts and liver. / Matalon, Reuben; Dorfman, A.

In: Journal of Clinical Investigation, Vol. 54, No. 4, 1974, p. 907-912.

Research output: Contribution to journalArticle

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AB - The Sanfilippo A syndrome is an autosomal recessive mucopolysaccharidosis characterized clinically by severe mental retardation and biochemically by storage in tissue and excretion in urine of excessive amounts of heparan sulfate. Since sulfamide groups are present in heparan sulfate, a sulfamidase deficiency could explain the impaired degradation of this polysaccharide. To investigate the enzymic basis of this disease, assays for sulfamidase were performed. Extracts of cultured fibroblasts and post mortem liver were prepared by suspension of tissues in acetate: NaCl buffer, pH 4.5, containing Triton X 100 (Rohm and Haas Co., Philadelphia, Pa.), sonication, and centrifugation at 10,000 g. The supernatant fluid was incubated with [35S] N sulfated heparin. The release of inorganic sulfate after 18 hr of incubation was determined by chromatography on Sephadex G 25. The liver and fibroblast extracts of patients with the Sanfilippo A syndrome showed a deficiency of sulfamidase. The quantity of heparan sulfate in fibroblasts derived from patients with Sanfilippo A, Hurler's and Hunter's diseases was found to be 7-10%, while it was about 1.25% of the total glycosaminoglycans in fibroblasts of normal controls.

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