PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 118467

Genetic complementation studies of multiple sulfatase deficiency.

A L Horwitz
View original source ↗Export metadata ↓

Abstract

Cultured fibroblasts from two individuals with multiple sulfatase deficiency (MSD) were found to have decreased activities of arylsulfatases (aryl-sulfate sulfohydrolase, EC 3.1.6.1) A, B, and C as well as iduronate-sulfate sulfatase, sulfamidase, and N-acetylglucosamine-6-sulfate sulfatase. The activity of N-acetylgalactosamine-6-sulfate sulfatase was decreased in one line but not in the other. Mixtures of MSD cell extracts with extracts from normal cells did not result in inhibition of normal sulfatase activities. Mixtures of MSD cell extracts with extracts of fibroblasts from patients with Hunter or Sanfilippo A syndrome did not activate iduronate-sulfate sulfatase or sulfamidase activity. Heterokaryons formed by fusion of MSD cells with Sanfilippo A fibroblasts demonstrated a partial correction of the enzyme deficiency. In similar manner, MSD-Hunter heterokaryons showed a significant increase in iduronate-sulfate-sulfatase activity. Genetic complementation in heterokaryons of MSD fibroblasts and cells of either Sanfilippo A or Hunter syndrome implies a genetic defect in MSD different from that causing specific sulfatase deficiencies.

Explore related subjects

ArylsulfatasesCells, CulturedGenetic Complementation TestHumansHybrid CellsLeukodystrophy, MetachromaticMucopolysaccharidosis IIMucopolysaccharidosis IIISulfatasesJournal ArticleResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A L Horwitz. 1979. Genetic complementation studies of multiple sulfatase deficiency.. https://doi.org/10.1073/pnas.76.12.6496

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1979

Is multiple sulphatase deficiency due to defective regulation of sulphohydrolase expression?

Multiple sulphatase deficiency disease is an unusual autosomal recessive disorder characterised biochemically by a deficiency of several sulphohydrolase activities. The laboratory diagnosis of this combined neurological connective tissue disorder is made on the basis of decreased activities of the lysosomal enzymes, arylsulphatase A and arylsulphatase B and the microsomal enzyme, arylsulphatase C. The primary defect in this multi-enzyme deficiency has not been identified. Using immunological techniques to characterise further the residual activities of arylsulphatases A and B in the multiple sulphatase deficiency disease, we have examined the levels of cross-reaching material (CRM) to arylsulphatases A and B in cultured skin fibroblasts from controls and patients with multiple sulphatase deficiency, metachromatic leukodystrophy (deficiency of only arylsulphatase A activity) and Maroteaux-Lamy syndrome (deficiency of only arylsulphatase B activity). We report here results indicating that arylsulphatases A and B in multiple sulphatase deficiency are reduced in their levels of CRM while retaining a normal activity/CRM ratio. Because the two enzymes are apparently structurally unrelated, these data are consistent with the possibility that their combined deficiencies in this disorder may result from a defect in the coordinated expression of sulphohydrolases.

Arylsulfatases↗
PubMed1979

Urinary excretion of arylsulfatases in malnourished/vitamin A deficient children.

Serum vitamin A (retinol) levels were generally low in all malnourished children (6-15 microgram/100 ml) compared with control children (50 microgram/100 ml). A significant increase in vitamin A after appropriate therapy was observed in all malnourished groups. Dietary supplements of proteins and calories even without extra vitamin A supplements increased serum vitamin A levels in cases of kwashiorkor indicating active mobilization of liver vitamin A. Total urinary arylsulfatase A activity excreted in 24-h or within 8-h in the morning (6 a.m. to 2 p.m.) was significantly reduced in cases of malnutrition with or without mild vitamin A deficiency symptoms. The excretion of arylsulfatase B was not altered. In cases of severe vitamin A deficiency coupled with malnutrition increased excretion of both arylsulfatases A and B was evident. These results on urinary arylsulfatases excretory pattern have been obtained either in samples collected for 24-h or specifically for 8-h (morning) and it is suggested that this test on urinary arylsulfatases may prove useful for detection of acute vitamin A deficiency with malnutrition in field studies. A ratio of arylsulfatases A/B of 2.0 or less seems to indicate mild malnutrition, the normal ratio being 3.4. Furthermore a low ratio coupled with increased excretion of both arylsulfatases A and B may be considered specific for acute vitamin A deficiency.

Arylsulfatases↗
PubMed1979

Clinical and biochemical investigations on patients with partial deficiency of placental steroid sulfatase.

We report on three independent cases with a partial deficiency of placental steroid sulfatase (E.C.3.1.6.2). Upon routine pregnancy monitoring these patients were detected on the basis of low estriol excretion and failing induction of labor. In all three cases a male was delivered and subsequently the diagnosis of partial deficiency of placental steroid sulfatase was confirmed enzymatically in placenta homogenates. In one case, fibroblast cultures were established from skin explants of mother and son. In fibroblasts of the child, as in placental tissue, the activity of steroid sulfatase was only 34% of normal. Similar values were obtained for arylsulfatase C, though this enzyme is clearly separable from steroid sulfatase by electrophoresis. In cells of the mother, enzyme activities were unremarkable.

Arylsulfatases↗