BACKGROUND: Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP). The infantile form features severe rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life threatening infantile HPP improved considerably after marrow cell transplantation.

OBJECTIVE: Our aim was to better understand and to advance these encouraging transplantation results.

DESIGN: In 1999, based on emerging mouse transplantation models involving implanted donor bone fragments as well as osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering a similar course of infantile HPP.

RESULTS: Four months later, radiographs demonstrated improved skeletal mineralization. Twenty months later, PCR analysis from adherent cells cultured from recipient bone suggested presence of small amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment. This patient, now 8 years old (7 years after transplantation), is active and growing, and has the clinical phenotype of the more mild childhood form of HPP.

CONCLUSIONS: Cumulative experience suggests that, after immune tolerance, donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form TNSALP replete osteoblasts that can improve mineralization.