Allogeneic bone marrow transplantation restores IGF-I production and linear growth in a gamma-SCID patient with abnormal growth hormone receptor signaling.

Severe combined immunodeficiency (SCID) is a heterogeneous group of disorders characterized by a severe defect of both T- and B-cell immunity, which generally require allogeneic bone marrow transplantation (BMT) within the first years of life. We previously reported a patient affected with an X-linked SCID due to L183S hemizygous missense gamma chain mutation, whose severe short stature was due to a peripheral growth hormone (GH) hyporesponsiveness associated to abnormal GH receptor (GH-R) signal transduction. In this study, we report the effect of BMT on the GH-R/insulin-like growth factor I (IGF-I) axis. After BMT, the patient showed a significant improvement in linear growth and normalization of basal- and GH-stimulated IGF-I values, which paralleled a fully competent immunological reconstitution. This suggests that cells derived from the hematopoietic stem cell may exert an unexpectedly significant role in producing IGF-I. This may also suggest that stem cell-based therapies may be useful for the correction of non-hematopoietic inherited disorders, such as those of GH-R/IGF-I axis.