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 gamma chain (gamma c) 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 gamma c in growth hormone (GH) receptor signaling, thus severe growth failure in XSCID may be related to the underlying gamma c defect.


OBJECTIVE
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.


CONCLUSIONS
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 gamma c defect may contribute to the severe growth failure in XSCID. This supports a role for defective gamma c in the extreme short stature of XSCID, and raises the possibility of recombinant IGF-I treatment to bypass this defect.
De Ravin
Suk See
SS
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD 20892, USA. sderavin@niaid.nih.gov
Shum
Elaine
E
Zarember
Kol A
KA
Rezvani
Geoffrey
G
Rosenfeld
Ron G
RG
Stratakis
Constantine A
CA
Malech
Harry L
HL
D000293:Adolescent; D001827:Body Height; D001835:Body Weight; D016026:Bone Marrow Transplantation; D002648:Child; D041321:Chromosomes, Human, X; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins; D012016:Reference Values; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I