Anemia in children with cartilage-hair hypoplasia is related to body growth and to the insulin-like growth factor system

Cartilage-hair hypoplasia (CHH) is a metaphyseal chondrodysplasia character ized by severe short-limbed short stature, hypoplastic hair, and defective immunity. The patients also have anemia. As GH may regulate both body growt h and erythropoiesis, we used CHH as a clinical model to study their interr elationships. Retrospective analysis of hematological data of 114 patients showed that th e severity of the anemia and macrocytosis in CHH Varies with age. The anemi a was most severe in early childhood. A prospective study of 21 patients wi th CHH showed that height correlates with hemoglobin (P = 0.006) and mean c orpuscular volume of red blood cells (P < 0.0001). The individual hemoglobi n levels correlated with the GH parameters [P = 0.035 for insulin-like grow th factor I (IGF-I) and P = 0.002 for IGF-binding protein-3], and the mean corpuscular volume of red blood cell values correlated with fetal hemoglobi n. Bone marrow cultures obtained from six patients with CHH showed reduced or totally absent erythroid colony formation, which was not influenced by G H or IGF-I in vitro or by GH treatment in vivo. In patients with CHH, we observed an association between erythropoiesis and growth. We conclude that body growth and erythropoiesis share common regul ators. One of these is the GH-IGF-I axis; other factors, as not yet identif ied, may also be important.