Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1971 Aug;123(5):883–894. doi: 10.1042/bj1230883

Hurler's, Hunter's and Morquio's syndromes. A biochemical study in the light of current views of the underlying defects

M F Dean 1, Helen Muir 1, R J F Ewins 1
PMCID: PMC1177089  PMID: 4256532

Abstract

Glycosaminoglycans were isolated from the urine of three patients with Hurler's, Hunter's and Morquio's syndromes and also from the liver and spleen of the case of Hurler's syndrome by a procedure avoiding further degradation. A method of determining the proportions of dermatan sulphate, heparan sulphate and chondroitin sulphate in each preparation is described. The relative proportions of these glycosaminoglycans in the urine and organs of the case of Hurler's syndrome were very similar. Glycosaminoglycans from the organs were of much lower molecular weight than normal, consisting of single chains of molecular weight about 5000 together with multiples of up to four such chains attached to peptide moieties. The linkage region normally attaching glycosaminoglycan chains to protein in whole protein–polysaccharides of connective tissue was degraded progressively towards serine. The total output and relative proportions of abnormal glycosaminoglycans in the urine were compared in two brothers with Hunter's syndrome examined on two occasions 4 years apart. At comparable ages they excreted about the same amount, and the relative proportions of each glycosaminoglycan remained essentially constant. The composition and chromatographic behaviour of the glycosaminoglycan in the urine from the case of Morquio's syndrome indicated that it consisted of material containing about one-third keratan sulphate and two-thirds chondroitin sulphate as part of the same molecule, as in proteoglycans of cartilage. The total output of glycosaminoglycans, although higher than normal, was considerably less than in other types of Mucopolysaccharidoses.

Full text

PDF
883

Selected References

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

  1. ANTONOPOULOS C. A., BORELIUS E., GARDELL S., HAMNSTROM B., SCOTT J. E. The precipitation of polyanions by long-chain aliphatic ammonium compounds. IV. Elution in salt solutions of mucopolysaccharide-quaternary ammonium complexes adsorbed on a support. Biochim Biophys Acta. 1961 Dec 9;54:213–226. doi: 10.1016/0006-3002(61)90360-2. [DOI] [PubMed] [Google Scholar]
  2. ANTONOPOULOS C. A., GARDELL S., SZIRMAI J. A., DETYSSONSK E. R. DETERMINATION OF GLYCOSAMINOGLYCANS (MUCOPOLYSACCHARIDES) FROM TISSUE ON THE MICROGRAM SCALE. Biochim Biophys Acta. 1964 Mar 2;83:1–19. doi: 10.1016/0926-6526(64)90045-x. [DOI] [PubMed] [Google Scholar]
  3. Antonopoulos C. A., Fransson L. A., Heinegård D., Gardell S. Chromatography of glycosaminoglycans on ECTEOLA-cellulose columns. Biochim Biophys Acta. 1967 Oct 9;148(1):158–163. doi: 10.1016/0304-4165(67)90291-7. [DOI] [PubMed] [Google Scholar]
  4. Aronson N. N., Jr, Davidson E. A. Lysosomal hyaluronidase from rat liver. I. Preparation. J Biol Chem. 1967 Feb 10;242(3):437–440. [PubMed] [Google Scholar]
  5. BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
  6. Bearn A. G. Symposium on mucopolysaccharidoses. Am J Med. 1969 Nov;47(5):661–663. doi: 10.1016/0002-9343(69)90161-2. [DOI] [PubMed] [Google Scholar]
  7. Borders C. L., Jr, Raftery M. A. Purification and partial characterization of testicular hyaluronidase. J Biol Chem. 1968 Jul 10;243(13):3756–3762. [PubMed] [Google Scholar]
  8. Bray B. A., Lieberman R., Meyer K. Structure of human skeletal keratosulfate. The linkage region. J Biol Chem. 1967 Jul 25;242(14):3373–3380. [PubMed] [Google Scholar]
  9. CALLANAN M. J., CARROLL W. R., MITCHELL E. R. Physical and chemical properties of protamine from the sperm of salmon (Oncorhynchus tschawytscha). J Biol Chem. 1957 Nov;229(1):279–287. [PubMed] [Google Scholar]
  10. Calatroni A., Donnelly P. V., Di Ferrante N. The glycosaminoglycans of human plasma. J Clin Invest. 1969 Feb;48(2):332–343. doi: 10.1172/JCI105989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clamp J. R., Dawson G., Hough L. The simultaneous estimation of 6-deoxy-L-galactose (L-fucose), D-mannose, D-galactose, 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine) and N-acetylneuraminic acid (sialic acid) in glycopeptides and glycoproteins. Biochim Biophys Acta. 1967 Nov 28;148(2):342–349. doi: 10.1016/0304-4165(67)90129-8. [DOI] [PubMed] [Google Scholar]
  12. Constantopoulos G., Dekaban A. S., Carroll W. R. Determination of molecular weight distribution of acid mucopolysaccharides by sephadex gel filtration. Anal Biochem. 1969 Oct 1;31(1):59–70. doi: 10.1016/0003-2697(69)90241-3. [DOI] [PubMed] [Google Scholar]
  13. Constantopoulos G. Hunter-Hurler syndrome: gel filtration and dialysis of urinary acid mucopolysaccharides. Nature. 1968 Nov 9;220(5167):583–585. doi: 10.1038/220583b0. [DOI] [PubMed] [Google Scholar]
  14. Dean M. F., Muir H. The characterization of a protein-polysaccharide isolated from Kurloff cells of the guinea pig. Biochem J. 1970 Aug;118(5):783–790. doi: 10.1042/bj1180783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Di Ferrante N. M. The measurement of urinary mucopolysaccharides. Anal Biochem. 1967 Oct;21(1):98–106. doi: 10.1016/0003-2697(67)90087-5. [DOI] [PubMed] [Google Scholar]
  16. Dorfman A., Matalon R. The Hurler and Hunter syndromes. Am J Med. 1969 Nov;47(5):691–707. doi: 10.1016/0002-9343(69)90164-8. [DOI] [PubMed] [Google Scholar]
  17. Dorner R. W., Antonopoulos C. A., Gardell S. Application of cetylpyridinium-complex elution methods to analysis of glycosaminoglycans of tendon. Biochim Biophys Acta. 1968 Jun 24;158(3):336–343. doi: 10.1016/0304-4165(68)90287-0. [DOI] [PubMed] [Google Scholar]
  18. Emanuel R. Genetics and congenital heart disease. Br Heart J. 1970 May;32(3):281–291. doi: 10.1136/hrt.32.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fransson L. A. Structure of dermatan sulfate. IV. Glycopeptides from the carbohydrate-protein linkage region of pig skin dermatan sulfate. Biochim Biophys Acta. 1968 Mar 11;156(2):311–316. [PubMed] [Google Scholar]
  20. Fratantoni J. C., Hall C. W., Neufeld E. F. The defect in Hurler and Hunter syndromes. II. Deficiency of specific factors involved in mucopolysaccharide degradation. Proc Natl Acad Sci U S A. 1969 Sep;64(1):360–366. doi: 10.1073/pnas.64.1.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fratantoni J. C., Hall C. W., Neufeld E. F. The defect in Hurler's and Hunter's syndromes: faulty degradation of mucopolysaccharide. Proc Natl Acad Sci U S A. 1968 Jun;60(2):699–706. doi: 10.1073/pnas.60.2.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gower W. E., Pedrini V. Age-related variations in proteinpolysaccharides from human nucleus pulposus, annulus fibrosus, and costal cartilage. J Bone Joint Surg Am. 1969 Sep;51(6):1154–1162. [PubMed] [Google Scholar]
  23. Heinegård D., Gardell S. Studies on protein-polysaccharide complex (proteoglycan) from human nucleus pulposus. I. Isolation and preliminary characterisation. Biochim Biophys Acta. 1967 Oct 9;148(1):164–171. doi: 10.1016/0304-4165(67)90292-9. [DOI] [PubMed] [Google Scholar]
  24. Helting T., Rodén L. Biosynthesis of chondroitin sulfate. I. Galactosyl transfer in the formation of the carbohydrate-protein linkage region. J Biol Chem. 1969 May 25;244(10):2790–2798. [PubMed] [Google Scholar]
  25. Helting T., Rodén L. Biosynthesis of chondroitin sulfate. II. Glucuronosyl transfer in the formation of the carbohydrate-protein linkage region. J Biol Chem. 1969 May 25;244(10):2799–2805. [PubMed] [Google Scholar]
  26. KAPLAN D., MEYER K. Ageing of human cartilage. Nature. 1959 May 2;183(4670):1267–1268. doi: 10.1038/1831267a0. [DOI] [PubMed] [Google Scholar]
  27. Kaplan D., McKusick V., Trebach S., Lazarus R. Keratosulfate-chondroitin sulfate peptide from normal urine and from urine of patients with Morquio syndrome (mucopolysaccharidosis IV). J Lab Clin Med. 1968 Jan;71(1):48–55. [PubMed] [Google Scholar]
  28. Knecht J., Cifonelli J. A., Dorfman A. Structural studies on heparitin sulfate of normal and Hurler tissues. J Biol Chem. 1967 Oct 25;242(20):4652–4661. [PubMed] [Google Scholar]
  29. LAURENT T. C., SCOTT J. E. MOLECULAR WEIGHT FRACTIONATION OF POLYANIONS BY CETYLPYRIDINIUM CHLORIDE IN SALT SOLUTIONS. Nature. 1964 May 16;202:661–662. doi: 10.1038/202661a0. [DOI] [PubMed] [Google Scholar]
  30. Lindahl U., Rodén L. The chondroitin 4-sulfate-protein linkage. J Biol Chem. 1966 May 10;241(9):2113–2119. [PubMed] [Google Scholar]
  31. Luscombe M., Phelps C. F. Action of degradative enzymes on the light fraction of bovine septa protein polysaccharide. Biochem J. 1967 Apr;103(1):103–109. doi: 10.1042/bj1030103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. MUIR H., MITTWOCH U., BITTER T. THE DIAGNOSTIC VALUE OF ISOLATED URINARY MUCOPOLYSACCHARIDES AND OF LYMPHOCYTE INCLUSIONS IN GARGOYLISM. Arch Dis Child. 1963 Aug;38:358–363. doi: 10.1136/adc.38.200.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. MUIR H. The nature of the link between protein and carbohydrate of a chondroitin sulphate complex from hyaline cartilage. Biochem J. 1958 Jun;69(2):195–204. doi: 10.1042/bj0690195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Matalon R., Dorfman A. Hurler's syndrome: biosynthesis of acid mucopolysaccharides in tissue culture. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1310–1316. doi: 10.1073/pnas.56.4.1310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mathews M. B., Cifonelli J. A. Comparative biochemistry of keratosulfates. J Biol Chem. 1965 Nov;240(11):4140–4145. [PubMed] [Google Scholar]
  36. Mathews M. B., Glagov S. Acid mucopolysaccharide patterns in aging human cartilage. J Clin Invest. 1966 Jul;45(7):1103–1111. doi: 10.1172/JCI105416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Muir H., Jacobs S. Protein-polysaccharides of pig laryngeal cartilage. Biochem J. 1967 May;103(2):367–374. doi: 10.1042/bj1030367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Muir H. The structure and metabolism of mucopolysaccharides (glycosaminoglycans) and the problem of the mucopolysaccharidoses. Am J Med. 1969 Nov;47(5):673–690. doi: 10.1016/0002-9343(69)90163-6. [DOI] [PubMed] [Google Scholar]
  39. Olsson I., Gardell S. Isolation and characterization of glycosaminoglycans from human leukocytes and platelets. Biochim Biophys Acta. 1967 Jul 25;141(2):348–357. doi: 10.1016/0304-4165(67)90109-2. [DOI] [PubMed] [Google Scholar]
  40. PEDRINI V., LENNZI L., ZAMBOTTI V. Isolation and identification of keratosulphate in urine of patients affected by Morquio-Ullrich disease. Proc Soc Exp Biol Med. 1962 Aug-Sep;110:847–849. doi: 10.3181/00379727-110-27668. [DOI] [PubMed] [Google Scholar]
  41. ROBINS M. M., STEVENS H. F., LINKER A. Morquio's disease: An abnormality of mucopolysaccharide metabolism. J Pediatr. 1963 Jun;62:881–889. doi: 10.1016/s0022-3476(63)80102-x. [DOI] [PubMed] [Google Scholar]
  42. SENO N., MEYER K., ANDERSON B., HOFFMAN P. VARIATIONS IN KERATOSULFATES. J Biol Chem. 1965 Mar;240:1005–1010. [PubMed] [Google Scholar]
  43. TREVELYAN W. E., HARRISON J. S. Studies on yeast metabolism. I. Fractionation and microdetermination of cell carbohydrates. Biochem J. 1952 Jan;50(3):298–303. doi: 10.1042/bj0500298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tsiganos C. P., Muir H. Estimation of pentoses and methylpentoses in biopolymers, in particular of fucose and xylose. Anal Biochem. 1966 Dec;17(3):495–501. doi: 10.1016/0003-2697(66)90184-9. [DOI] [PubMed] [Google Scholar]
  45. Tsiganos C. P., Muir H. Studies on protein-polysaccharides from pig laryngeal cartilage. Heterogeneity, fractionation and characterization. Biochem J. 1969 Aug;113(5):885–894. doi: 10.1042/bj1130885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. VON NOORDEN G. K., ZELLWEGER H., PONSETI I. V. Ocular findings in Morquio-Ullrich's disease. With report of two cases. Arch Ophthalmol. 1960 Oct;64:585–591. doi: 10.1001/archopht.1960.01840010587017. [DOI] [PubMed] [Google Scholar]
  47. Wasteson A. A method for the determination of molecular weight dispersion in chondroitin sulphate on a microgram level. Biochim Biophys Acta. 1969 Feb 18;177(1):152–154. doi: 10.1016/0304-4165(69)90076-2. [DOI] [PubMed] [Google Scholar]
  48. Wessler E. Analytical and preparative separation of acidic glycosaminoglycans by electrophoresis in barium acetate. Anal Biochem. 1968 Dec;26(3):439–444. doi: 10.1016/0003-2697(68)90205-4. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES