Avaliação do crescimento de indivíduos com anemia falciforme: aspectos endócrinos, bioquímicos e moleculares

Abstract

Sickle cell anemia (SCA) has severe and multisystem clinical manifestations. The complications of SCA are inversely proportional to fetal hemoglobin (HbF) concentrations, among other modifying factors, with emphasis on co-inheritance of alpha-thalassemia. Although the SCA does not affect embryonic growth, at two years of age can be noted a deficit in weight and stature, which will gradually accentuate, with greater prominence for the adolescence stage, when the pubertal delay accentuates the difference between the weight and height of children with SCA compared to healthy controls. Growth impairment of children with SCA includes several causes such as tissue hypoxia, anemia, vaso-occlusion, malnutrition, recurrent infections, hypogonadism, growth hormone (GH) deficiency or abnormalities in the growth hormone/insuline-like growth factor 1 (GH/IGF1) axis. Hydroxyurea (HU) therapy has been affecting the reduction of adult and child morbidity and mortality. In this research, we longitudinally evaluated the growth profile, the effectiveness of HU therapy in attenuating growth impairment, the role of the GH/IGF1 axis, and the influence of modifying factors, such as HbF and alpha-thalassemia, in children from 3 to 12 years with SCA. The study involved 39 patients registered in the unit blood center of Governador Valadares of the Hemominas Foundation with a mean age of 8.2 ± 2.2 years, 51.3% (n = 20) male and 64.1% (n = 25) under treatment with HU. The z-score of children's height was -0.75 ± 1.1, and 15.4% (n = 6) of them had serum IGF1 levels adjusted by chronological age (CA) below normal. The prevalence of short stature in children was 10.3% (n = 4), although among parents it was 14.4% (n = 11). Evaluating the difference between z-score/height of parents and z-score/height of children, we found greater impairment in height of children in relation to the genetic target in those with shorter height, lower prediction of final height (PFH) calculated by bone age (BA) and alpha-thalassemia co-inheritance. On the other hand, when the GH/IGF1 axis was assessed by the z-score/IGF1 and z-score/IGFBP3, adjusted for CA or BA, there was a significant greater impairment of the axis in children with lower body mass index (BMI), greater delay in BA compared to CA , higher serum levels of thyroid stimulating hormone (TSH), shorter stature, lower HbF level, co-inheritance of alpha-thalassemia and use of HU for a short period. In conclusion, although the height of children with SCA was not impaired in relation to the height of parents, there was a group of children with greater impairment of their growth potential. Among the possible factors associated with height impairment in this portion of children with AF are co-inheritance of alpha-thalassemia, lower HbF ratio, higher TSH levels, lower BMI, delayed BA, and use of UH for less than one year. These factors were associated with lower GH / IGF1 axis efficiency.