Summary
An 11-year-old girl with mucopolysaccharidosis I Scheie phenotype (MPS I-S) received a bone marrow transplant (BMT) from her heterozygous HLA-identical LMC-non-reactive mother. Multidisciplinary studies were carried out and results evaluated 21 months after transplantation. Herein we report the ultrastructural findings pre-and post-BMT in skin. Multidisciplinary studies are commonly used to evaluate the benefits of metabolic correction following BMT in some MPS and other inherited metabolic disorders, and changes in morphology have been described in liver and few other tissues. In this case, we elected skin, since connective tissue is universally involved in MPS and is safely and easily obtainable. Comparison of skin biopsy specimens taken before and after BMT showed a considerable change in dermal fibroblast morphology, with marked reduction in cell size and the number and size of abnormal lysosomes, thus indicating the clearance of storage. Our results demonstrate that dermal cells respond to enzyme replacement therapy in MPS I-S, with the clearance of glycosaminoglycan lysosomal accumulation in connective tissue fibroblasts, which had near-normal morphology 21 months after BMT. Therefore, the practice of skin biopsy after BMT in MPS and other metabolic disorders in which dermal cells are involved should be encouraged.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Belcher RW (1972) Ultrastructure of the skin in the genetic mucopolysaccharidoses. Arch Pathol 94:511–518
Bioulac P, Mercier M, Beylot C, Fontan D (1975) The diagnosis of mucopolysaccharidoses by electron microscopy of skin biopsies. J Cutan Pathol 2:179–190
de Groote CM (1988) Het Electronmicroscopisch Onderzoek van Huidbiopten als Bijdrage in de Diagnostick van Metabole Aandoeningen van het Zenuwstelsel. Thesis, Born-Bunge Stichting. Universiteit Antwerpen, Belgium
Gasper PW, Thrall MA, Wenger DA, Mercy DW, Ham L, Dornsife RE, MCBiles K, Quackenbush SL, Kesel ML, Gilette EL, Hoover EA (1984) Correction of feline arylsulphatase B deficiency (mucopolysaccharidosis VI) by bone marrow transplantation. Nature 312:467–469
Hobbs JR, Hugh-Jones K, Barrett AJ, Byrom N, Chambers D, Henry K, James DCO, Lucas CF, Rogers TR, Benson PF, Tansley LR, Patrick AD, Mossman J, Young EP (1981) Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet II:709–712
Hopwood JJ, Muller V, Smithson A, Baggett N (1979) A fluorimetric assay using 4-methylumbelliferyl-alpha-iduronide for the estimation of alpha-L-iduronidase activity and the detection of Hurler and Scheie syndromes. Clin Chim Acta 92:257–265
Hugh-Jones K, Hobbs J, Chambers D, White S, Byrom N, Williamson S, Barrett J, Kristin H, Patrick D (1984) Bone marrow transplantation in mucopolysaccharidosis. In: Barranger JA, Brady RO (eds) Molecular basis of lysosomal storage disorders. Academic Press, New York, pp 411–428
Krivit W, Pierpont ME, Ayaz K, Tsai M, Ramsay NKC, Kersey JH, Weisdorf S, Sibley R, Mc Govern MM, Schwartz M, Desnick RJ (1984) Bone marrow transplantation in Maroteaux-Lamy disease (mucopolysaccharidosis VI): correction of the enzymatic defect. N Engl J Med 31:1606–1611
Lowry OM, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:165–275
Martin JJ, Ceuterick C, Leroy JV (1976) Contribution de la biopsie cutanée au diagnostic des encéphalopathies métaboliques. Rev Neurol (Paris) 132:639–651
Martin JJ, Ceuterick C (1983) Prenatal pathology in mucopolysaccharidosis; comparison with postnatal cases. Clin Neuropathol 2:122–127
McGovern MM, Ludman MD, Short MP, Steinfeld L, Katan M, Raab EL, Krivit W, Desnick RJ (1986) Bone marrow transplantation in Maroteaux-Lamy syndrome (MPS type 6): status 40 months after BMT. Birth Defects 22:41–53
Navarro C, Sancho S (1988) Valor de la biopsia de piel y conjuntiva en el diagnóstico de las enfermedades lisosomales de depósito. Patologia 21:1–6
Neufeld EF (1980) The uptake of enzymes into lysosomes: an overview. Birth Defects 16:77–84
Neufeld E, Muenzer J (1989) The mucopolysaccharidoses. In: Scriver CR, Baudet AL, Sly WS, Valle D (eds) Stanbury metabolic basis of inherited disease, 6th edn, McGraw-Hill, New York pp 1565–1573
Roubicek M, Gehler J, Spranger J (1985) The clinical spectrum of alpha-L-iduronidase deficiency. Am J Med Genet 20:471–481
Wengwe DA, Gasper PW, Thrall MA, Dial Sh M, LeCouteur RA, Hoover EA (1986) Bone marrow transplantation in the feline model of arylsulfatase B deficiency. Birth Defects 22:177–186
Whitley ChB, Ramsay NKC, Kersey H, Krivit W (1986) Bone marrow transplantation for Hurler syndrome: assessment of metabolic correction. Birth Defects 22:7–24
Author information
Authors and Affiliations
Additional information
Supported in part by Fondo de Investigaciones Sanitarias de la Seguridad Social Grant 89/0389. Clinical aspects of this report were presented in Munich, September 1989, at the 27th Annual Meeting of the Society for the Study of Inborn Errors of Metabolism, and also at “Réunion de la Société Française de Neuropathologie” held in Toulouse, July 1990
Rights and permissions
About this article
Cite this article
Navarro, C., Dominguez, C., Costa, M. et al. Bone marrow transplant in a case of mucopolysaccharidosis I Scheie phenotype: skin ultrastructure before and after transplantation. Acta Neuropathol 82, 33–38 (1991). https://doi.org/10.1007/BF00310920
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00310920