Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1983 Apr;36(4):415–430. doi: 10.1136/jcp.36.4.415

Biochemical and histopathological studies on patients with mucopolysaccharidoses, two of whom had been treated by fibroblast transplantation.

J Crow, D A Gibbs, W Cozens, E Spellacy, R W Watts
PMCID: PMC498237  PMID: 6403596

Abstract

Biochemical and pathological observations on tissues from two patients with Hurler disease (mucopolysaccharidosis IH; alpha-L-iduronidase deficiency) who had been treated by fibroblast transplants as a means of enzyme replacement treatment are reported. These results and those obtained in three surgical specimens [ligamentum flavum with dura mater from a case of Scheie disease (mucopolysaccharidosis IS; alpha-L-iduronidase deficiency); a fetus with Hurler disease; and tonsil from a patient with Hunter disease (mucopolysaccharidosis II; alpha-L-idurono-2-sulphate sulphatase deficiency)] illustrate the inadequacy of routine histological processing to demonstrate the abnormal glycosaminoglycan accumulation in this group of diseases. A combined approach using histochemistry and electron microscopy enables the extent of both extracellular and intracellular involvement to be assessed. The fetus (20 wk gestation) already showed evidence of Hurler disease. The pathological appearances in both of the fibroblast-transplanted patients were those which would have been expected in patients dying with unmodified Hurler disease. There was no detectable alpha-L-iduronidase activity in the brain, liver, kidney or in fibroblasts cultured from either the transplantation sites or from remote subcutaneous sites in either of the transplanted patients. These results are discussed from the viewpoint of their bearing on the pathophysiology of the mucopolysaccharidoses and proposals for their treatment by enzyme replacement.

Full text

PDF
415

Images in this article

421Image
on p.421
421Image
on p.421
423Image
on p.423
423Image
on p.423
423Image
on p.423
423Image
on p.423
423Image
on p.423
423Image
on p.423
424Image
on p.424
425Image
on p.425
425Image
on p.425
426Image
on p.426
427Image
on p.427

Selected References

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

  1. BISHTON R. L., NORMAN R. M., TINGEY A. The pathology and chemistry of a case of gargoylism. J Clin Pathol. 1956 Nov;9(4):305–315. doi: 10.1136/jcp.9.4.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belcher R. W. Ultrastructure and function of eccrine glands in the mucopolysaccharidoses. Arch Pathol. 1973 Nov;96(5):339–341. [PubMed] [Google Scholar]
  3. Belcher R. W. Ultrastructure of the skin in the genetic mucopolysaccharidoses. Arch Pathol. 1972 Dec;94(6):511–518. [PubMed] [Google Scholar]
  4. Cotlier E. Letter: Corneal cloudiness and retinitis pigmentosa in the mucopolysaccharidoses. N Engl J Med. 1975 Apr 10;292(15):812–812. doi: 10.1056/NEJM197504102921521. [DOI] [PubMed] [Google Scholar]
  5. Crawfurd M., Dean M. F., Hunt D. M., Johnson D. R., MacDonald R. R., Muir H., Wright E. A., Wright C. R. Early prenatal diagnosis of Hurler's syndrome with termination of pregnancy and confirmatory findings on the fetus. J Med Genet. 1973 Jun;10(2):144–153. doi: 10.1136/jmg.10.2.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DAWSON I. M. The histology and histochemistry of gargoylism. J Pathol Bacteriol. 1954 Apr;67(2):587–604. doi: 10.1002/path.1700670232. [DOI] [PubMed] [Google Scholar]
  7. Dean M. F., Muir H., Benson P. F., Button L. R., Boylston A., Mowbray J. Enzyme replacement therapy by fibroblast transplantation in a case of Hunter syndrome. Nature. 1976 May 27;261(5558):323–325. doi: 10.1038/261323a0. [DOI] [PubMed] [Google Scholar]
  8. Dean M. F., Muir H., Benson P. F., Button L. R. Enzyme replacement therapy by transplantation of HLA-compatible fibroblasts in Sanfilippo A syndrome. Pediatr Res. 1981 Jun;15(6):959–963. doi: 10.1203/00006450-198106000-00016. [DOI] [PubMed] [Google Scholar]
  9. Dean M. F., Stevens R. L., Muir H., Benson P. F., Button L. R., Anderson R. L., Boylston A., Mowbray J. Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome. J Clin Invest. 1979 Jan;63(1):138–146. doi: 10.1172/JCI109267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dekaban A. S., Constantopoulos G., Herman M. M., Steusing J. K. Mucopolysaccharidosis type V. (Scheie syndrome). A postmortem study by multidisciplinary techniques with emphasis on the brain. Arch Pathol Lab Med. 1976 May;100(5):237–245. [PubMed] [Google Scholar]
  11. Dekaban A. S., Constantopoulos G. Mucopolysaccharidosis type I, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain. Acta Neuropathol. 1977 Jul 15;39(1):1–7. doi: 10.1007/BF00690379. [DOI] [PubMed] [Google Scholar]
  12. Dorling J. Localisation of sulphated glycosaminoglycans in the mucopolysaccharidoses by a simple technique using cryostat sections. J Clin Pathol. 1980 Sep;33(9):897–898. doi: 10.1136/jcp.33.9.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Doshi R., Sandry S. A., Churchill A. W., Brownell B. The cerebellum in mucopolysaccharidosis. A histological, histochemical, and ultrastructural study. J Neurol Neurosurg Psychiatry. 1974 Oct;37(10):1133–1138. doi: 10.1136/jnnp.37.10.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eliahu R., Sekeles E., Cohen R., Bach G. The correction of Hunter fibroblasts by exogenous iduronate sulfate sulfatase: biochemical and ultrastructural studies. Am J Hum Genet. 1981 Jul;33(4):576–583. [PMC free article] [PubMed] [Google Scholar]
  15. Elsner B. Ultrastructure of the rectal wall in Hunter's syndrome. Gastroenterology. 1970 Jun;58(6):856–862. [PubMed] [Google Scholar]
  16. François J. Ocular manifestations of the mucopolysaccharidoses. Ophthalmologica. 1974;169(5):345–361. doi: 10.1159/000307137. [DOI] [PubMed] [Google Scholar]
  17. Gibbs D. A., Spellacy E., Roberts A. E., Watts R. W. The treatment of lysosomal storage diseases by fibroblast transplantation: some preliminary observations. Birth Defects Orig Artic Ser. 1980;16(1):457–474. [PubMed] [Google Scholar]
  18. Gibbs D. A., Watts R. W. The identification of the enzymes that catalyse the oxidation of glyoxylate to oxalate in the 100000 g supernatant fraction of human hyperoxaluric and control liver and heart tissue. Clin Sci. 1973 Mar;44(3):227–241. doi: 10.1042/cs0440227. [DOI] [PubMed] [Google Scholar]
  19. HAMBRICK G. W., Jr, SCHEIE H. G. Studies of the skin in Hurler's syndrome: mucopolysaccharidosis. Arch Dermatol. 1962 Apr;85:455–471. doi: 10.1001/archderm.1962.01590040019002. [DOI] [PubMed] [Google Scholar]
  20. Hadfield M. G., Ghatak N. R., Nakoneczna I., Lippman H. R., Myer E. C., Constantopoulos G., Bradley R. M. Pathologic findings in mucopolysaccharidosis type IIIB (Sanfilippo's sydnrome B). Arch Neurol. 1980 Oct;37(10):645–650. doi: 10.1001/archneur.1980.00500590069012. [DOI] [PubMed] [Google Scholar]
  21. Hall C. W., Neufeld E. F. Alpha-L-iduronidase activity in cultured skin fibroblasts and amniotic fluid cells. Arch Biochem Biophys. 1973 Oct;158(2):817–821. doi: 10.1016/0003-9861(73)90577-8. [DOI] [PubMed] [Google Scholar]
  22. Hobbs J. R., Hugh-Jones K., Barrett A. J., Byrom N., Chambers D., Henry K., James D. C., Lucas C. F., Rogers T. R., Benson P. F. Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet. 1981 Oct 3;2(8249):709–712. doi: 10.1016/s0140-6736(81)91046-1. [DOI] [PubMed] [Google Scholar]
  23. Hug G. Pre- and postnatal pathology, enzyme treatment, and unresolved issues in five lysosomal disorders. Pharmacol Rev. 1978 Dec;30(4):565–591. [PubMed] [Google Scholar]
  24. 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]
  25. JEANLOZ R. W. The nomenclature of mucopolysaccharides. Arthritis Rheum. 1960 Jun;3:233–237. doi: 10.1002/art.1780030306. [DOI] [PubMed] [Google Scholar]
  26. Kenyon K. R., Quigley H. A., Hussels I. E., Wyllie R. G., Goldberg M. F. The systemic mucopolysaccharidoses. Ultrastructural and histochemical studies of conjunctiva and skin. Am J Ophthalmol. 1972 Jun;73(6):811–833. [PubMed] [Google Scholar]
  27. Kint J. A., Dacremont G., Carton D., Orye E., Hooft C. Mucopolysaccharidosis: secondarily induced abnormal distribution of lysosomal isoenzymes. Science. 1973 Jul 27;181(4097):352–354. doi: 10.1126/science.181.4097.352. [DOI] [PubMed] [Google Scholar]
  28. Kresse H., Paschke E., von Figura K., Gilberg W., Fuchs W. Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6822–6826. doi: 10.1073/pnas.77.11.6822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kriel R. L., Hauser W. A., Sung J. H., Posalaky Z. Neuroanatomical and electroencephalographic correlations in Sanfilippo syndrome, type A. Arch Neurol. 1978 Dec;35(12):838–843. doi: 10.1001/archneur.1978.00500360062013. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Loeb H., Jonniaux G., Resibois A., Cremer N., Dodion J., Tondeur M., Gregoire P. E., Richard J., Cieters P. Biochemical and ultrastructural studies in Hurler's syndrome. J Pediatr. 1968 Dec;73(6):860–874. doi: 10.1016/s0022-3476(68)80239-2. [DOI] [PubMed] [Google Scholar]
  32. Maynard J. A., Cooper R. R., Ponseti I. V. Morquio's disease (mucopolysaccharidosis type IV). Ultrastructure of epiphyseal plates. Lab Invest. 1973 Feb;28(2):194–205. [PubMed] [Google Scholar]
  33. Niermeijer M. F., Halley D., Sachs E., Tichelaar-Klepper C., Garver K. L. Transport and storage of amniotic fluid samples for prenatal diagnosis of metabolic diseases. Humangenetik. 1973;20(2):175–178. doi: 10.1007/BF00284856. [DOI] [PubMed] [Google Scholar]
  34. Olsen I., Dean M. F., Harris G., Muir H. Direct transfer of a lysosomal enzyme from lymphoid cells to deficient fibroblasts. Nature. 1981 May 21;291(5812):244–247. doi: 10.1038/291244a0. [DOI] [PubMed] [Google Scholar]
  35. Pennock C. A. A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses. J Clin Pathol. 1976 Feb;29(2):111–123. doi: 10.1136/jcp.29.2.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rome L. H., Weissmann B., Neufeld E. F. Direct demonstration of binding of a lysosomal enzyme, alpha-L-iduronidase, to receptors on cultured fibroblasts. Proc Natl Acad Sci U S A. 1979 May;76(5):2331–2334. doi: 10.1073/pnas.76.5.2331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Spellacy E., Bankes J. L., Crow J., Dourmashkin R., Shah D., Watts R. W. Glaucoma in a case of Hurler disease. Br J Ophthalmol. 1980 Oct;64(10):773–778. doi: 10.1136/bjo.64.10.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Spellacy E., Gibbs D. A., Watts R. W. A newly recognized syndrome of connective tissue dysplasia in siblings (previously described as a variant of Morquio disease). Q J Med. 1981 Autumn;50(200):377–415. [PubMed] [Google Scholar]
  39. Spicer S. S., Garvin A. J., Simson J. A., Wertelecki V. Cytochemistry of the skin of patients with mucopolysaccharidoses. Histochem J. 1978 Mar;10(2):137–150. doi: 10.1007/BF01003299. [DOI] [PubMed] [Google Scholar]
  40. Spicer S. S., Garvin A. J., Wohltmann H. J., Simson J. A. The ultrastructure of the skin in patients with mucopolysaccharidoses. Lab Invest. 1974 Nov;31(5):488–502. [PubMed] [Google Scholar]
  41. Watts R. W., Spellacy E., Kendall B. E., du Boulay G., Gibbs D. A. Computed tomography studies on patients with mucopolysaccharidoses. Neuroradiology. 1981 Feb;21(1):9–23. doi: 10.1007/BF00518788. [DOI] [PubMed] [Google Scholar]
  42. Winters P. R., Harrod M. J., Molenich-Heetred S. A., Kirkpatrick J., Rosenberg R. N. alpha-L-iduronidase deficiency and possible Hurler-Scheie genetic compound. Clinical, pathologic, and biochemical findings. Neurology. 1976 Nov;26(11):1003–1007. doi: 10.1212/wnl.26.11.1003. [DOI] [PubMed] [Google Scholar]

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

RESOURCES