European Journal of Pediatrics

, Volume 147, Issue 6, pp 634–638 | Cite as

Multiple sulfatase deficiency with a novel biochemical presentation

  • G. Constantopoulos
Case Reports


Deficient activities of cerebroside-sulfatase, N-Acetylgalactosamine-4-sulfatase and iduronide 2-sulfatase in the lymphocytes of a patient suspected of metachromatic leukodystrophy, established the diagnosis of multiple sulfatase deficiency (MSD). Cultured skin fibroblasts (of early passage) from the patient had normal levels of activity for the three sulfatases. One week after the first examination, the activities of the three sulfatases in the fibroblasts of the patient declined and within a month were 4%–29% of normal. Total urinary glycosaminoglycans were within normal range. However, further examination showed an increase in the concentration of heparan sulfate, which comprised more than 50% of the total, compared with less than 20% in normal controls. Urinary sulfatides, cholesterol esters, cholesterol, and triglycerides were increased. The results from the study of this unique case of MSD suggest that time-dependent changes affect the activities of sulfatases in MSD. These results also demonstrate the necessity of assaying the sulfatases in both lymphocytes and fibroblasts from suspected cases of MSD.

Key words

Multiple sulfatase deficiency Sulfatases Glycosaminoglycans Metachromatic leukodystrophy 



multiple sulfatase deficiency


metachromatic leukodystrophy






cetylpyridinium chloride


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Austin JH (1973) Studies in metachromatic leukodystrophy XII. Multiple sulfatase deficiency. Arch Neurol 28:258–264Google Scholar
  2. 2.
    Austin JH, Armstrong D, Shearer L (1965) 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. Arch Neurol 13:594–614Google Scholar
  3. 3.
    Bharucha BA, Naik G, Savliwala AS, Joshi RM, Kumta NB (1984) Siblings with the Austin variant of metachromatic leukodystrophy multiple sulfatidosis. Indian J Pediatr 51:477–480Google Scholar
  4. 4.
    Bischel M, Austin J, Kemeny H (1966) Metachromatic leukodystrophy VII. Elevated sulfated acid polysaccharide levels in urine and postmortem tissues. Arch Neurol 15:13–28Google Scholar
  5. 5.
    Blumenkrantz N, Asboe-Hansen G (1973) New method for quantitative determination of uronic acids. Anal Biochem 54:484–489Google Scholar
  6. 6.
    Chang PL, Rosa NE, Ballantyne SR, Davidson RG (1983) Biochemical variability of Arylsulphatases-A,-B and-C in cultured fibroblasts from patients with multiple sulphatase deficiency. J Inherited Metab Dis 6:167–172Google Scholar
  7. 7.
    Constantopoulos G, Dekaban AS (1975) Chemical definition of the mucopolysaccharidoses. Clin Chim Acta 59:321–336Google Scholar
  8. 8.
    Constantopoulos G, McComb RD, Dekaban AS (1976) Neurochemistry of the mucopolysaccharidoses: Brain glycosaminoglycans in normals and four types of mucopolysaccharidoses. J Neurochem 26:901–908Google Scholar
  9. 9.
    Di Ferrante NM (1967) The measurement of urinary mucopolysaccharides. Anal Biochem 21:98–106Google Scholar
  10. 10.
    Di Ferrante N, Neri G, Neri ME, Hogsett WE, III. (1972) Measurement of urinary glycosaminoglycans with quarternary ammonium salts: an extension of the method. Connect Tissue Res 1:93–101Google Scholar
  11. 11.
    Eto Y, Numaguchi S, Handa T (1979) Urinary acid mucopolysaccharides in multiple sulfatase deficiency (Mucosulfatidosis). Eur J Pediatr 132:207–211Google Scholar
  12. 12.
    Eto Y, Tokoro T, Handa T, Herschkowitz NN, Rennert OM (1982) Acid mucopolysaccharide (AMPS) abnormality in multiple sulfatase deficiency: chemical compositions of AMPS in urine and liver. Pediatr Res 16:395–399Google Scholar
  13. 13.
    Fedde K, Horwitz AL (1984) Complementation of multiple sulfatase deficiency in somatic cell hybrids. Am J Hum Genet 36:623–633Google Scholar
  14. 14.
    Hall CW, Liebaers I, Di Natale P, Neufeld EF (1978) Enzymic diagnosis of the genetic mucopolysaccharide storage disorders. Methods Enzymol 50:439–456Google Scholar
  15. 15.
    Kolodny EH, Moser HW (1983) Sulfatide lipidosis: Metachromatic leukodystrophy. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS (eds) The metabolic basis of inherited disease, 5th ed. McGraw-Hill, New York, pp 881–905Google Scholar
  16. 16.
    Lakatos M, Di Ferrante N (1974) Simple measurement of urinary glycosaminoglycans and degradation products. Biochem Med 9:256–260Google Scholar
  17. 17.
    Lowry OH, Rosebrough NT, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  18. 18.
    Minami R, Fujibayashi S, Tachi N, Wagatsuma K, Nakao T, Ikeno T, Tsugawa S, Sukegawa K, Orii T (1983) Activities of sulfatases for the degradation of acidic glycosaminoglycans in cultured skin fibroblasts from two siblings with multiple sulfatase deficiency. Clin Chim Acta 129:175–180Google Scholar
  19. 19.
    Murphy JV, Wolfe HJ, Balazs EA, Moser HW (1971) A patient with deficiency of arylsulfatase A, B, C and steroid sulfatase, associated with storage of sulfatide, cholesterol sulfate and glycosaminoglycans. In: Bernsohn J, Grossman HJ (eds) Lipid storage diseases: enzymatic defects and clinical implications. Academic Press, New York, pp 67–110Google Scholar
  20. 20.
    Nevsimalova S, Elleder M, Smid F, Zemankova M (1984) Multiple sulfatase deficiency in homozygotic twins. J Inherited Metab Dis 7:38–40Google Scholar
  21. 21.
    Perlmutter-Cremer N, Libert J, Vamos E, Spehl M, Liebaers I (1981) Unusual early manifestation of multiple sulfatase deficiency. Ann Radiol 24:43–48Google Scholar
  22. 22.
    Schiller S, Slover GA, Dorfman A (1961) A method for the separation of acid mucopolysaccharides: its application to the isolation of heparin from the skin of rats. J Biol Chem 236:983–987Google Scholar
  23. 23.
    Steckel F, Hasilik A, von Figura K (1985) Synthesis and stability of arylsulfatase A and B in fibroblasts from multiple sulfatase deficiency. Eur J Biochem 151:141–145Google Scholar
  24. 24.
    Steckel F, Hasilik A, von Figura K (1985) multiple sulfatase deficiency: Degradation of arylsulfatase A and B after endocytosis in fibroblasts. Eur J Biochem 151:147–152Google Scholar
  25. 25.
    Suzuki K (1978) Enzymic diagnosis of Sphingolipidoses. Methods Enzymol 50:456–488Google Scholar
  26. 26.
    von Figura K, Hasilik A, Steckel F (1984) Lysosomal storage disorders caused by instability of the missing enzymes. In: Brady RO, Barranger JA (eds) Molecular basis of lysosomal storage disorders. Academic Press, New York, pp 133–146Google Scholar
  27. 27.
    Waheed A, Hasilik A, von Figura K (1982) Enhanced breakdown of arylsulfatase A in multiple sulfatase deficiency. Eur J Biochem 123:317–321Google Scholar
  28. 28.
    Warshawsky L, King J, Burns G, Horwitz AL (1985) Rapid degradation of arylsulfatase C1 (steroid sulfatase) in multiple sulfatase deficiency. Am J Hum Genet 37: A21Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • G. Constantopoulos
    • 1
  1. 1.Developmental and Metabolic Neurology Branch, National Institute of Neurological and Communicative Disorders and StrokeNational Institutes of HealthBethesda

Personalised recommendations