Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1976 Feb;29(2):111–123. doi: 10.1136/jcp.29.2.111

A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses.

C A Pennock
PMCID: PMC475987  PMID: 132459

Abstract

The current state of knowledge on the biochemical abnormalities in the mucopolysaccharidoses is reviewed. Methods for the estimation and identification of glycoasminoglycans excreted in the mucopolysaccharidoses are discussed and a selection of simple and reliable methods of value in a small hospital laboratory have been given in detail in an appendix.

Full text

PDF
111

Selected References

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

  1. BERRY H. K., SPINANGER J. A paper spot test useful in study of Hurler's syndrome. J Lab Clin Med. 1960 Jan;55:136–138. [PubMed] [Google Scholar]
  2. 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]
  3. BRIMACOMBE J. S., STACEY M. MUCOPOLYSACCHARIDES IN DISEASE. Adv Clin Chem. 1964;7:199–234. doi: 10.1016/s0065-2423(08)60375-3. [DOI] [PubMed] [Google Scholar]
  4. Bach G., Eisenberg F., Jr, Cantz M., Neufeld E. F. The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase. Proc Natl Acad Sci U S A. 1973 Jul;70(7):2134–2138. doi: 10.1073/pnas.70.7.2134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bach G., Friedman R., Weissmann B., Neufeld E. F. The defect in the Hurler and Scheie syndromes: deficiency of -L-iduronidase. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2048–2051. doi: 10.1073/pnas.69.8.2048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berenson G. S., Dalferes E. R., Jr Urinary excretion of mucopolysaccharides in normal individuals and in the Marfan syndrome. Biochim Biophys Acta. 1965 Jul 1;101(2):183–192. doi: 10.1016/0926-6534(65)90049-7. [DOI] [PubMed] [Google Scholar]
  7. Berman E. R., Vered J., Bach G. A reliable spot test for mucopolysaccharidoses. Clin Chem. 1971 Sep;17(9):886–890. [PubMed] [Google Scholar]
  8. Bitter T., Siegenthaler P., DePreux T., Martin E. Excretion in the urine of aminoacridine precipitable polyuronides (acid mucopolysaccharides) in patients with rheumatoid arthritis. Ann Rheum Dis. 1970 Jul;29(4):427–433. doi: 10.1136/ard.29.4.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CARSON N. A., NEILL D. W. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child. 1962 Oct;37:505–513. doi: 10.1136/adc.37.195.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cantz M., Chrambach A., Bach G., Neufeld E. F. The Hunter corrective factor. Purification and preliminary characterization. J Biol Chem. 1972 Sep 10;247(17):5456–5462. [PubMed] [Google Scholar]
  11. Cantz M., Chrambach A., Neufeld E. F. Characterization of the factor deficient in the Hunter syndrome by polyacrylamide gel electrophoresis. Biochem Biophys Res Commun. 1970 Jun 5;39(5):936–942. doi: 10.1016/0006-291x(70)90414-6. [DOI] [PubMed] [Google Scholar]
  12. Carter C. H., Wan A. T., Carpenter D. G. Commonly used tests in the detection of Hurler's syndrome. J Pediatr. 1968 Aug;73(2):217–221. doi: 10.1016/s0022-3476(68)80071-x. [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. DI FERRANTE N. Acid mucopolysaccharides of normal human urine. J Lab Clin Med. 1963 Apr;61:633–641. [PubMed] [Google Scholar]
  15. DI FERRANTE N., RICH C. The mucopolysaccharide of normal human urine. Clin Chim Acta. 1956 Nov-Dec;1(6):519–524. doi: 10.1016/0009-8981(56)90039-0. [DOI] [PubMed] [Google Scholar]
  16. DI FERRANTE N., ROBBINS W. C., RICH C. Urinary excretion of acid mucopolysaccharides by patients with lupus erythematosus. J Lab Clin Med. 1957 Dec;50(6):897–900. [PubMed] [Google Scholar]
  17. DORFMAN A. Studies on the biochemistry of connective tissue. Pediatrics. 1958 Sep;22(3):576–589. [PubMed] [Google Scholar]
  18. Dean M. F., Muir H., Ewins R. J. Hurler's, Hunter's and Morquio's syndromes. A biochemical study in the light of current views of the underlying defects. Biochem J. 1971 Aug;123(5):883–894. doi: 10.1042/bj1230883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Di Ferrante N., Lipscomb H. S. Urinary glycosaminoglycans versus creatinine excretion: a used and abused parameter. Clin Chim Acta. 1970 Oct;30(1):69–72. doi: 10.1016/0009-8981(70)90194-4. [DOI] [PubMed] [Google Scholar]
  21. Dorfman A., Lorincz A. E. OCCURRENCE OF URINARY ACID MUCOPOLYSACCHARIDES IN THE HURLER SYNDROME. Proc Natl Acad Sci U S A. 1957 Jun 15;43(6):443–446. doi: 10.1073/pnas.43.6.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fratantoni J. C., Hall C. W., Neufeld E. F. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science. 1968 Nov 1;162(3853):570–572. doi: 10.1126/science.162.3853.570. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Goldberg J. M., Cotlier E. Specific isolation and analysis of mucopolysaccharides (glycosaminoglycans) from human urine. Clin Chim Acta. 1972 Oct;41:19–27. doi: 10.1016/0009-8981(72)90491-3. [DOI] [PubMed] [Google Scholar]
  25. Hardingham T. E., Phelps C. F. The glycosaminoglycans of neonatal rat skin. Biochem J. 1970 May;117(5):813–818. doi: 10.1042/bj1170813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hata R., Nagai Y. A rapid and micro method for separation of acidic glycosaminoglycans by two-dimensional electrophoresis. Anal Biochem. 1972 Feb;45(2):462–468. doi: 10.1016/0003-2697(72)90208-4. [DOI] [PubMed] [Google Scholar]
  27. Humbel R., Chamoles N. A. Sequential thin layer chromatography of urinary acidic glycosaminglycans. Clin Chim Acta. 1972 Aug;40(1):290–293. doi: 10.1016/0009-8981(72)90287-2. [DOI] [PubMed] [Google Scholar]
  28. JEANLOZ R. W. The nomenclature of mucopolysaccharides. Arthritis Rheum. 1960 Jun;3:233–237. doi: 10.1002/art.1780030306. [DOI] [PubMed] [Google Scholar]
  29. Jenkins P., Davies G. R., Harper P. S. Morquio-Brailsford disease. A report of four affected sisters with absence of excessive keratan sulphate in the urine. Br J Radiol. 1973 Sep;46(549):668–675. doi: 10.1259/0007-1285-46-549-668. [DOI] [PubMed] [Google Scholar]
  30. Kaplan D. Classification of the mucopolysaccharidoses based on the pattern of mucopolysacchariduria. Am J Med. 1969 Nov;47(5):721–729. doi: 10.1016/0002-9343(69)90166-1. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Kresse H. Mucopolysaccharidosis 3 A (Sanfilippo A disease): deficiency of a heparin sulfamidase in skin fibroblasts and leucocytes. Biochem Biophys Res Commun. 1973 Oct 1;54(3):1111–1118. doi: 10.1016/0006-291x(73)90807-3. [DOI] [PubMed] [Google Scholar]
  33. Linker A., Evans L. R., Langer L. O. Morquio's disease and mucopolysaccharide excretion. J Pediatr. 1970 Dec;77(6):1039–1047. doi: 10.1016/s0022-3476(70)80089-0. [DOI] [PubMed] [Google Scholar]
  34. Lippiello L., Mankin H. J. Thin-layer chromatographic separation of the isomeric chondroitin sulfates, dermatan sulfate, and keratan sulfate. Anal Biochem. 1971 Jan;39(1):54–58. doi: 10.1016/0003-2697(71)90460-x. [DOI] [PubMed] [Google Scholar]
  35. MEYER K., GRUMBACH M. M., LINKER A., HOFFMAN P. Excretion of sulfated mucopolysaccharides in gargoylism (Hurler's syndrome). Proc Soc Exp Biol Med. 1958 Feb;97(2):275–279. doi: 10.3181/00379727-97-23714. [DOI] [PubMed] [Google Scholar]
  36. Manley G., Hawksworth J. Diagnosis of Hurler's syndrome in the hospital laboratory and the determination of its genetic type. Arch Dis Child. 1966 Feb;41(215):91–96. doi: 10.1136/adc.41.215.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Manley G., Severn M., Hawksworth J. Excretion patterns of glycosaminoglycans and glycoproteins in normal human urine. J Clin Pathol. 1968 May;21(3):339–345. doi: 10.1136/jcp.21.3.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Maroteaux P. Différenciation biochimique des maladies de Hurler et de Hunter par fractionnement de l'héparitine sulfate. Rev Eur Etud Clin Biol. 1970 Feb;15(2):203–205. [PubMed] [Google Scholar]
  39. Matalon R., Arbogast B., Justice P., Brandt I. K., Dorfman A. Morquio's syndrome: deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase. Biochem Biophys Res Commun. 1974 Nov 27;61(2):759–765. doi: 10.1016/0006-291x(74)91022-5. [DOI] [PubMed] [Google Scholar]
  40. Matalon R., Dorfman A. Hurler's syndrome, an -L-iduronidase deficiency. Biochem Biophys Res Commun. 1972 May 26;47(4):959–964. doi: 10.1016/0006-291x(72)90586-4. [DOI] [PubMed] [Google Scholar]
  41. McKusick V. A., Kaplan D., Wise D., Hanley W. B., Suddarth S. B., Sevick M. E., Maumanee A. E. The genetic mucopolysaccharidoses. Medicine (Baltimore) 1965 Nov;44(6):445–483. doi: 10.1097/00005792-196511000-00001. [DOI] [PubMed] [Google Scholar]
  42. McKusick V. A. The nosology of the mucopolysaccharidoses. Am J Med. 1969 Nov;47(5):730–747. doi: 10.1016/0002-9343(69)90167-3. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Murphy D., Pennock C. A., London K. J. Gas-liquid chromatographic measurement of glucosamine and galactosamine content of urinary glycosaminoglycans. Clin Chim Acta. 1974 Jun 19;53(2):145–152. doi: 10.1016/0009-8981(74)90092-8. [DOI] [PubMed] [Google Scholar]
  45. O'Brien J. S. Sanfilippo syndrome: profound deficiency of alpha-acetylglucosaminidase activity in organs and skin fibroblasts from type-B patients. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1720–1722. doi: 10.1073/pnas.69.7.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Oliver M. F. Thrombosis and oestrogens. Lancet. 1967 Sep 2;2(7514):510–511. doi: 10.1016/s0140-6736(67)91679-0. [DOI] [PubMed] [Google Scholar]
  47. 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]
  49. Pennock C. A. A modified screening test for glycosaminoglycan excretion. J Clin Pathol. 1969 May;22(3):379–380. doi: 10.1136/jcp.22.3.379-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Pennock C. A., Charles R. G., Stansbie D. Glycosaminoglycan fractions in normal human urine. Ann Clin Biochem. 1975 Sep;12(5):207–211. doi: 10.1177/000456327501200152. [DOI] [PubMed] [Google Scholar]
  51. Pennock C. A., Mott M. G., Batstone G. F. Screening for mucopolysaccharidoses. Clin Chim Acta. 1970 Jan;27(1):93–97. doi: 10.1016/0009-8981(70)90379-7. [DOI] [PubMed] [Google Scholar]
  52. Pennock C. A., Wharton B. A., White F. Urinary glycosaminoglycan excretion in the neonatal period. Acta Paediatr Scand. 1971 May;60(3):299–300. doi: 10.1111/j.1651-2227.1971.tb06660.x. [DOI] [PubMed] [Google Scholar]
  53. Pennock C. A., White F., Murphy D., Charles R. G., Kerr H. Excess glycosaminoglycan excretion in infancy and childhood. Acta Paediatr Scand. 1973 Sep;62(5):481–491. doi: 10.1111/j.1651-2227.1973.tb08141.x. [DOI] [PubMed] [Google Scholar]
  54. Pennock C. A., White F., Wharton B. A. CPC precipitable uronic acid: creatinine ratio in random urine samples collected from normal children. Acta Paediatr Scand. 1972 Mar;61(2):125–127. doi: 10.1111/j.1651-2227.1972.tb15914.x. [DOI] [PubMed] [Google Scholar]
  55. Procopis P. G., Turner B., Ruxton J. T., Brown D. A. Screening tests for mucopolysaccharidosis. J Ment Defic Res. 1968 Mar;12(1):13–17. doi: 10.1111/j.1365-2788.1968.tb00237.x. [DOI] [PubMed] [Google Scholar]
  56. 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]
  57. Renuart A. W. Screening for inborn errors of metabolism associated with mental deficiency or neurologic disorders or both. N Engl J Med. 1966 Feb 17;274(7):384–387. doi: 10.1056/NEJM196602172740705. [DOI] [PubMed] [Google Scholar]
  58. Robertson W. V., Harvey J. The determination of galactose in urinary acidic glycosaminoglycans as a measure of keratan sulfate-like substances in urine. Biochem Med. 1972 Jun;6(3):246–256. doi: 10.1016/0006-2944(72)90045-2. [DOI] [PubMed] [Google Scholar]
  59. Rosenfeld L. Quantitative levels of the constituents of acid mucopolysaccharides and other carbohydrate polymers in dialyzed normal human urine. Clin Chim Acta. 1971 Jan;31(1):263–269. doi: 10.1016/0009-8981(71)90385-8. [DOI] [PubMed] [Google Scholar]
  60. SCOTT J. E. Aliphatic ammonium salts in the assay of acidic polysaccharides from tissues. Methods Biochem Anal. 1960;8:145–197. doi: 10.1002/9780470110249.ch4. [DOI] [PubMed] [Google Scholar]
  61. SEGNI G., ROMANO C., TORTOROLO G. DIAGNOSTIC TEST FOR GARGOYLISM. Lancet. 1964 Aug 22;2(7356):420–420. doi: 10.1016/s0140-6736(64)90442-8. [DOI] [PubMed] [Google Scholar]
  62. Sjöberg I., Fransson L. A., Matalon R., Dorfman A. Hunter's syndrome: a deficiency of L-idurono-sulfate sulfatase. Biochem Biophys Res Commun. 1973 Oct 1;54(3):1125–1132. doi: 10.1016/0006-291x(73)90809-7. [DOI] [PubMed] [Google Scholar]
  63. Sly W. S., Quinton B. A., McAlister W. H., Rimoin D. L. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973 Feb;82(2):249–257. doi: 10.1016/s0022-3476(73)80162-3. [DOI] [PubMed] [Google Scholar]
  64. Spranger J. W. Biochemical definition of the mucopolysaccharidoses. Z Kinderheilkd. 1970;108(1):17–31. doi: 10.1007/BF00440562. [DOI] [PubMed] [Google Scholar]
  65. Stumpf D. A., Austin J. H., Crocker A. C., LaFrance M. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). I. Sulfatase B deficiency in tissues. Am J Dis Child. 1973 Dec;126(6):747–755. doi: 10.1001/archpedi.1973.02110190597003. [DOI] [PubMed] [Google Scholar]
  66. TELLER W. M., BURKE E. C., ROSEVEAR J. W., McKENZIE B. F. Urinary excretion of acid mucopolysaccharides in normal children and patients with gargoylism. J Lab Clin Med. 1962 Jan;59:95–101. [PubMed] [Google Scholar]
  67. Teller W. M., Ziemann A. Thin layer chromatography of urinary acid glycosaminoglycans as screening procedure for mucopolysaccharidoses. Horm Metab Res. 1969 Jan;1(1):32–35. doi: 10.1055/s-0028-1095171. [DOI] [PubMed] [Google Scholar]
  68. VANHOOF F., HERS H. G. L'ULTRASTRUCTURE LES CELLULES H'EPATIQUES DANS LA MALADIE DE HUERLER (GARGOYLISME) C R Hebd Seances Acad Sci. 1964 Aug 3;259:1281–1283. [PubMed] [Google Scholar]
  69. Valdivieso F., Martinez-Valverde A., Maties M., Ugarte M. Early diagnosis of hypermucopolysacchariduria. Clin Chim Acta. 1973 Mar 30;44(3):357–600. doi: 10.1016/0009-8981(73)90078-8. [DOI] [PubMed] [Google Scholar]
  70. 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]
  71. Wessler E. Determination of acidic glycosaminoglycans (mucopolysaccharides) in urine by an ion exchange method. Application to "collagenoses", gargoylism, the nail-patella syndrome and Farber's disease. Clin Chim Acta. 1967 May;16(2):235–243. doi: 10.1016/0009-8981(67)90186-6. [DOI] [PubMed] [Google Scholar]
  72. Whiteman P. The quantitative determination of glycosaminoglycans in urine with Alcian Blue 8GX. Biochem J. 1973 Feb;131(2):351–357. doi: 10.1042/bj1310351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Whiteman P. The quantitative measurement of Alcian Blue-glycosaminoglycan complexes. Biochem J. 1973 Feb;131(2):343–350. doi: 10.1042/bj1310343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wiesmann U., Neufeld E. F. Scheie and Hurler syndromes: apparent identity of the biochemical defect. Science. 1970 Jul 3;169(3940):72–74. doi: 10.1126/science.169.3940.72. [DOI] [PubMed] [Google Scholar]
  75. Wusteman F. S., Lloyd A. G., Dodgson K. S. Thin-layer chromatography and the rapid identification of common acidic glycosaminoglycans. J Chromatogr. 1966 Jan;21(1):32–39. doi: 10.1016/s0021-9673(01)91257-9. [DOI] [PubMed] [Google Scholar]
  76. di Ferrante N., Donnelly P. V., Berglund R. K. Colorimetric measurement of dermatan sulphate. Biochem J. 1971 Sep;124(3):549–553. doi: 10.1042/bj1240549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. von Figura K., Lögering M., Mersmann G., Kresse H. Sanfilippo B disease: serum assays for detection of homozygous and heterozygous individuals in three families. J Pediatr. 1973 Oct;83(4):607–611. doi: 10.1016/s0022-3476(73)80222-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES