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Children with sickle cell anemia (SCA) frequently have short stature. We propose that alterations in the IGF-I axis are involved in their growth failure. We investigated the IGF-I axis in children with SCA and height below the 25th percentile (n = 15) and compared it with that of children with SCA and height above the 50th percentile (n = 7). IGF-I and IGFBP-3 levels were assessed by RIA. IGFBP-3 proteolysis was assessed by a protease activity assay and by Western immunoblots. IGF-I and IGFBP-3 SDS were low for both groups. In the short statured patients, IGF-I SDS correlated with height velocity SDS (p = 0.018). IGFBP-3 SDS, when corrected for bone age, decreased with age (p = 0.0054). IGFBP-3 was proteolyzed in both groups although the short statured patients had lower levels of absolute intact IGFBP-3 when compared with the normally growing group (p = 0.028). We demonstrated that children with SCA have abnormalities in the IGF-I axis, which worsen with age.

Short Stature in Children with Sickle Cell Anemia Correlates with Alterations in the IGF-I Axis