Hematopoietic stem cell transplantation for metabolic storage diseases

Almost thirty years of hematopoietic cell transplantation for congenital enzymopathies have revealed that the transfer of relatively few hematopoietic stem cells is able to fully reconstitute the lymphohematopoietic system in conditioned recipients and to maintain long term complementation of the enzyme defect in the recipient. Despite decades of effort to illuminate the mechanisms whereby the cross correction occurs, it remains unclear why hematopoietic cell transplantation is adequate only in some enzyme deficiencies. Here we review both biochemical and clinical data on the metabolic storage diseases in which the natural history and quality of life have been changed after hematopoietic cell transplantation. The challenge ahead is to understand the pathophysiology of congenital enzymopathies resistant to correction with hematopoietic cell transplantation, and to test whether the advances in stem cell therapy and gene correction can be translated into less toxic and even more effective therapy of metabolic storage diseases for which hematopoietic cell transplantation is a standard of care today.