Long-term outcome of Hurler syndrome following bone marrow transplantation

Chester B Whitley, Kumar G Belani, P. N. Chang, Carole G Summers, Bruce R Blazar, Michael Y Tsai, R. E. Latchaw, N. K.C. Ramsay, J. H. Kersey

Research output: Contribution to journalArticle

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Abstract

Previous reports suggested a therapeutic response of lysosomal storage diseases such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long-term follow-up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA-identical sib donor between September 1983- October 1988. Follow-up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte α- L-iduronidase level, measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was a survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8-8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte α-L-iduronidase at levels reflecting the donor genotype and degree of donor engraftment. Urinary glycosaminoglycan excretion declined to near-normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressure >20 cm CSF); however, all surviving children attained normal or near-normal pressure within 18 months of donor engraftment. Long-term follow-up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by successful engraftment. Early transplantation of children with Hurler syndrome who have normal intelligence is likely to have the clearest benefit because long-term intellectual outcome will be limited by brain damage which has occurred prior to treatment.

Original languageEnglish (US)
Pages (from-to)209-218
Number of pages10
JournalAmerican Journal of Medical Genetics
Volume46
Issue number2
DOIs
StatePublished - Jan 1 1993

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Mucopolysaccharidosis I
Bone Marrow Transplantation
Tissue Donors
Iduronidase
Cerebrospinal Fluid Pressure
Survivors
Brain
Leukocytes
Transplantation
Tomography
Lysosomal Storage Diseases
Intracranial Hypertension
Attention Deficit Disorder with Hyperactivity
Hydrocephalus
Child Development
Glycosaminoglycans
Intelligence
Psychometrics
Neuroimaging
Atrophy

Keywords

  • glycosaminoglycan
  • hydrocephalus
  • mucopolysaccharidosis
  • neurologic disease

Cite this

Long-term outcome of Hurler syndrome following bone marrow transplantation. / Whitley, Chester B; Belani, Kumar G; Chang, P. N.; Summers, Carole G; Blazar, Bruce R; Tsai, Michael Y; Latchaw, R. E.; Ramsay, N. K.C.; Kersey, J. H.

In: American Journal of Medical Genetics, Vol. 46, No. 2, 01.01.1993, p. 209-218.

Research output: Contribution to journalArticle

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