Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1969 Mar;62(3):887–891. doi: 10.1073/pnas.62.3.887

METACHROMATIC LEUKODYSTROPHY: ARYLSULFATASE-A DEFICIENCY IN SKIN FIBROBLAST CULTURES*

Myna T Porter 1, Arvan L Fluharty 1, Hayato Kihara 1
PMCID: PMC223681  PMID: 5257010

Abstract

Fibroblasts cultured from the skin of a patient with metachromatic leukodystrophy have been found to manifest the biochemical defect of this inborn error of metabolism, a deficiency of arylsulfatase A. Diseased cells had less than five per cent of normal arylsulfatase-A activity, while activities of other lysosomal enzymes—including arylsulfatase B, β-galactosidase, β-glucuronidase, and β-N-acetylglucosaminidase—were comparable to those in control cells. The presence of dissociable inhibitors in extracts of the diseased cells was excluded by combination experiments. The deficiency of the enzyme in leukocytes was also confirmed and is comparable to that found in cultured fibroblasts. The finding that readily cultured fibroblasts from easily obtained skin biopsy specimens exhibit the enzymatic defect should prove valuable in the biochemical study of this disease.

Full text

PDF
887

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AUSTIN J. H. Metachromatic form of diffuse cerebral sclerosis. III. Significance of sulfatide and other lipid abnormalities in white matter and kidney. Neurology. 1960 May;10:470–483. doi: 10.1212/wnl.10.5.470. [DOI] [PubMed] [Google Scholar]
  2. AUSTIN J., MCAFEE D., SHEARER L. METACHROMATIC FORM OF DIFFUSE CEREBRAL SCLEROSIS. IV. LOW SULFATASE ACTIVITY IN THE URINE OF NINE LIVING PATIENTS WITH METACHROMATIC LEUKODYSTROPHY (MLD). Arch Neurol. 1965 May;12:447–455. doi: 10.1001/archneur.1965.00460290003001. [DOI] [PubMed] [Google Scholar]
  3. Austin J., Armstrong D., Shearer L., McAfee D. Metachromatic form of diffuse cerebral sclerosis. VI. A rapid test for the sulfatase A deficiency in metachromatic leukodystrophy (MLD) urine. Arch Neurol. 1966 Mar;14(3):259–269. doi: 10.1001/archneur.1966.00470090031004. [DOI] [PubMed] [Google Scholar]
  4. Austin J., Armstrong D., Shearer L. Metachromatic form of diffuse cerebral sclerosis. V. The nature and significance of low sulfatase activity: a controlled study of brain, liver and kidney in four patients with metachromatic leukodystrophy (MLD). Arch Neurol. 1965 Dec;13(6):593–614. doi: 10.1001/archneur.1965.00470060029003. [DOI] [PubMed] [Google Scholar]
  5. BAUM H., DODGSON K. S., SPENCER B. The assay of arylsulphatases A and B in human urine. Clin Chim Acta. 1959 May;4(3):453–455. doi: 10.1016/0009-8981(59)90119-6. [DOI] [PubMed] [Google Scholar]
  6. Cravioto H., O'Brien J., Lockwood R., Kasten F. H., Booher J. Metachromatic leukodystrophy (sulfatide lipidoses) cultured in vitro. Science. 1967 Apr 14;156(3772):243–245. doi: 10.1126/science.156.3772.243. [DOI] [PubMed] [Google Scholar]
  7. DODGSON K. S., ROSE F. A., TUDBALL N. Studies on sulphatases. 23. The enzymic desulphation of tyrosine O-sulphate. Biochem J. 1959 Jan;71(1):10–15. doi: 10.1042/bj0710010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Danes B. S., Bearn A. G. Hurler's syndrome: demonstration of an inherited disorder of connective tissue in cell culture. Science. 1965 Aug 27;149(3687):987–989. doi: 10.1126/science.149.3687.987. [DOI] [PubMed] [Google Scholar]
  9. Gatt S., Rapport M. M. Isolation of beta-galactosidase and beta-glucosidase from brain. Biochim Biophys Acta. 1966 Mar 7;113(3):567–576. doi: 10.1016/s0926-6593(66)80014-0. [DOI] [PubMed] [Google Scholar]
  10. JATZKEWITZ H. [Leukodystrophy, Scholz' type, (metachromatic form of diffuse sclerosis) with sphinolipoidosis (cerebroside-sulfuric acid ester storage disease)]. Hoppe Seylers Z Physiol Chem. 1960 May 31;318:265–277. doi: 10.1515/bchm2.1960.318.1.265. [DOI] [PubMed] [Google Scholar]
  11. Kampine J. P., Brady R. O., Kanfer J. N., Feld M., Shapiro D. Diagnosis of gaucher's disease and niemann-pick disease with small samples of venous blood. Science. 1967 Jan 6;155(3758):86–88. doi: 10.1126/science.155.3758.86. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. MEHL E., JATZKEWITZ H. EVIDENCE FOR THE GENETIC BLOCK IN METACHROMATIC LEUCODYSTROPHY (ML). Biochem Biophys Res Commun. 1965 May 3;19:407–411. doi: 10.1016/0006-291x(65)90137-3. [DOI] [PubMed] [Google Scholar]
  14. MORGAN J. F., MORTON H. J., PARKER R. C. Nutrition of animal cells in tissue culture; initial studies on a synthetic medium. Proc Soc Exp Biol Med. 1950 Jan;73(1):1–8. doi: 10.3181/00379727-73-17557. [DOI] [PubMed] [Google Scholar]
  15. Mehl E., Jatzkewitz H. Cerebroside 3-sulfate as a physiological substrate of arylsulfatase A. Biochim Biophys Acta. 1968 Mar 25;151(3):619–627. doi: 10.1016/0005-2744(68)90008-9. [DOI] [PubMed] [Google Scholar]
  16. Ockerman P. A. Acid hydrolases in skin and plasma in gargoylism. Deficiency of beta-galactosidase in skin. Clin Chim Acta. 1968 Apr;20(1):1–6. doi: 10.1016/0009-8981(68)90375-6. [DOI] [PubMed] [Google Scholar]
  17. Percy A. K., Brady R. O. Metachromatic leukodystrophy: diagnosis with samples of venous blood. Science. 1968 Aug 9;161(3841):594–595. doi: 10.1126/science.161.3841.594. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES