Short stature in partially corrected x-linked severe combined immunodeficiency - Suboptimal response to growth hormone

Background: X-linked severe combined immunodeficiency (XSCID) results from defects in the common cytokine receptor γ chain (γc) required for signaling by receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21. Following haploidentical bone marrow transplant without myelo-conditioning for XSCID, most patients achieve partial reconstitution often limited to T lymphocytes. Many partially corrected patients manifest extreme short stature (<5th percentile). Previous reports have implicated γc in growth hormone (GH) receptor signaling, thus severe growth failure in XSCID may be related to the underlying γc defect. Aim: To evaluate the GH/insulin-like growth factor-I (IGF-I) axis in three children with XSCID and partial immune reconstitution with profound growth failure. Methods: The IGF-I generation test was performed by administering recombinant GH subcutaneously for 5 days, and measuring serum levels for IGF-I before GH injection, and on days 5 and 8. Results: Study of the somatotropic axis revealed profoundly diminished IGF-I production following rGH challenge in all three patients. Conclusion: The data indicate that the GH/IGF-I axis in these partially corrected XSCID patients with severe short stature is profoundly impaired, and supports previous studies suggesting that the underlying γc defect may contribute to the severe growth failure in XSCID. This supports a role for defective γc in the extreme short stature of XSCID, and raises the possibility of recombinant IGF-I treatment to bypass this defect.