Skip to main content
PMC home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 1987 Oct;62(10):1044–1049. doi: 10.1136/adc.62.10.1044

Bone marrow transplantation in the treatment of alpha-mannosidosis.

A Will 1, A Cooper 1, C Hatton 1, I B Sardharwalla 1, D I Evans 1, R F Stevens 1
PMCID: PMC1778651  PMID: 3314721

Abstract

Bone marrow transplantation was performed in a patient with alpha-mannosidosis. To our knowledge this is the first time such treatment has been attempted. The patient died 18 weeks after successful grafting and specimens of tissues were obtained at necropsy. Alpha-mannosidase activity in spleen and liver was just below normal (spleen 102 mumol/g/hour, control 113-330; liver 29 mumol/g/hour, control 30-131). Splenic alpha-mannosidase activity was indistinguishable from the control enzyme with respect to the Michaelis constant, heat stability, and inhibition by cobalt ions, as was 86% of the liver enzyme. In brain tissue alpha-mannosidase activity was 7% of controls, and less than one third had the properties of the normal enzyme. Oligosaccharides were present only in small amounts in liver and spleen, whereas they were greatly increased in brain tissue. Electron microscopic pictures of liver and spleen tissue showed normal morphology, but brain tissue showed definite vacuolation. These findings suggest that transplantation reversed the somatic changes of alpha-mannosidosis but did not affect lysosomal storage within brain tissue. It is concluded that marrow transplantation may not be a suitable treatment for alpha-mannosidosis.

Full text

PDF
1046

Images in this article

1046Fig 2
on p.1046
1047Fig 6a
on p.1047
1047Fig 6b
on p.1047

Selected References

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

  1. Autio S., Nordén N. E., Ockerman P. A., Riekkinen P., Rapola J., Louhimo T. Mannosidosis: clinical, fine-structural and biochemical findings in three cases. Acta Paediatr Scand. 1973 Nov;62(6):555–565. doi: 10.1111/j.1651-2227.1973.tb17065.x. [DOI] [PubMed] [Google Scholar]
  2. Aylsworth A. S., Taylor H. A., Stuart C. M., Thomas G. H. Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents. J Pediatr. 1976 May;88(5):814–818. doi: 10.1016/s0022-3476(76)81120-1. [DOI] [PubMed] [Google Scholar]
  3. Bayever E., Ladisch S., Philippart M., Brill N., Nuwer M., Sparkes R. S., Feig S. A. Bone-marrow transplantation for metachromatic leucodystrophy. Lancet. 1985 Aug 31;2(8453):471–473. doi: 10.1016/s0140-6736(85)90402-7. [DOI] [PubMed] [Google Scholar]
  4. Desnick R. J., Sharp H. L., Grabowski G. A., Brunning R. D., Quie P. G., Sung J. H., Gorlin R. J., Ikonne J. U. Mannosidosis: clinical, morphologic, immunologic, and biochemical studies. Pediatr Res. 1976 Dec;10(12):985–996. doi: 10.1203/00006450-197612000-00008. [DOI] [PubMed] [Google Scholar]
  5. Gordon B. A., Carson R., Haust M. D. Unusual clinical and ultrastructural features in a boy with biochemically typical mannosidosis. Acta Paediatr Scand. 1980 Nov;69(6):787–792. doi: 10.1111/j.1651-2227.1980.tb07154.x. [DOI] [PubMed] [Google Scholar]
  6. Jolly R. D., Thompson K. G., Murphy C. E., Manktelow B. W., Bruere A. N., Winchester B. G. Enzyme replacement therapy--an experiment of nature in a chimeric mannosidosis calf. Pediatr Res. 1976 Apr;10(4):219–224. doi: 10.1203/00006450-197604000-00003. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Matsuura F., Nunez H. A., Grabowski G. A., Sweeley C. C. Structural studies of urinary oligosaccharides from patients with mannosidosis. Arch Biochem Biophys. 1981 Apr 1;207(2):337–352. doi: 10.1016/0003-9861(81)90041-2. [DOI] [PubMed] [Google Scholar]
  9. Sakiyama T., Tsuda M., Owada M., Joh K., Miyawaki S., Kitagawa T. Bone marrow transplantation for Niemann-Pick mice. Biochem Biophys Res Commun. 1983 Jun 15;113(2):605–610. doi: 10.1016/0006-291x(83)91769-2. [DOI] [PubMed] [Google Scholar]
  10. Taylor H. A., Thomas G. H., Aylsworth A., Stevenson R. E., Reynolds L. W. Mannosidosis: deficiency of a specific alpha-mannosidase component in cultured fibroblasts. Clin Chim Acta. 1975 Feb 22;59(1):93–99. doi: 10.1016/0009-8981(75)90223-5. [DOI] [PubMed] [Google Scholar]
  11. Taylor R. M., Farrow B. R., Stewart G. J., Healy P. J. Enzyme replacement in nervous tissue after allogeneic bone-marrow transplantation for fucosidosis in dogs. Lancet. 1986 Oct 4;2(8510):772–774. doi: 10.1016/s0140-6736(86)90299-0. [DOI] [PubMed] [Google Scholar]
  12. Wenger D. A., Gasper P. W., Thrall M. A., Dial S. M., LeCouteur R. A., Hoover E. A. Bone marrow transplantation in the feline model of arylsulfatase B deficiency. Birth Defects Orig Artic Ser. 1986;22(1):177–186. [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES