Presented in part at the 20th Annual Meeting of the American Society for Bone and Mineral Research, December 1-6, 1998, San Francisco, CA, USA.
Marrow Cell Transplantation for Infantile Hypophosphatasia†
Version of Record online: 1 APR 2003
Copyright © 2003 ASBMR
Journal of Bone and Mineral Research
Volume 18, Issue 4, pages 624–636, April 2003
How to Cite
Whyte, M. P., Kurtzberg, J., McALISTER, W. H., Mumm, S., Podgornik, M. N., Coburn, S. P., Ryan, L. M., Miller, C. R., Gottesman, G. S., Smith, A. K., Douville, J., Waters-Pick, B., Armstrong, R. D. and Martin, P. L. (2003), Marrow Cell Transplantation for Infantile Hypophosphatasia. J Bone Miner Res, 18: 624–636. doi: 10.1359/jbmr.2003.18.4.624
The authors have no conflict of interest.
- Issue online: 2 DEC 2009
- Version of Record online: 1 APR 2003
- Manuscript Accepted: 29 OCT 2002
- Manuscript Revised: 21 OCT 2002
- Manuscript Received: 10 JUN 2002
- alkaline phosphatase;
- stem cells
An 8-month-old girl who seemed certain to die from the infantile form of hypophosphatasia, an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), underwent the first trial of bone marrow cell transplantation for this heritable type of rickets. After cytoreduction, she was given T-cell-depleted, haplo-identical marrow from her healthy sister. Chimerism in peripheral blood and bone marrow became 100% donor. Three months later, she was clinically improved, with considerable healing of rickets and generalized skeletal remineralization. However, 6 months post-transplantation, worsening skeletal disease recurred, with partial return of host hematopoiesis. At the age of 21 months, without additional chemotherapy or immunosuppressive treatment, she received a boost of donor marrow cells expanded ex vivo to enrich for stromal cells. Significant, prolonged clinical and radiographic improvement followed soon after. Nevertheless, biochemical features of hypophosphatasia have remained unchanged to date. Skeletal biopsy specimens were not performed. Now, at 6 years of age, she is intelligent and ambulatory but remains small. Among several hypotheses for our patient's survival and progress, the most plausible seems to be the transient and long-term engraftment of sufficient numbers of donor marrow mesenchymal cells, forming functional osteoblasts and perhaps chondrocytes, to ameliorate her skeletal disease.