Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia

We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent beta-thalassemia (beta-TDT). We considered 68 beta-TDT patients (11.98 +/- 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network. Iron overload was quantified by T2* technique and biventricular function by cine images. Replacement myocardial fibrosis was evaluated by late gadolinium enhancement technique. Three groups of patients were identified: homozygous beta+ (N = 19), compound heterozygous beta 0 beta+ (N = 24), and homozygous beta 0 (N = 25). The homozygous beta 0 group showed significantly lower global heart and pancreas T2* values than the homozygous beta+ group. Compared to patients with homozygous beta+ genotype, beta 0 beta+ as well as beta 0 beta 0 patients were more likely to have pancreatic iron overload (odds ratio = 6.53 and 10.08, respectively). No difference was detected in biventricular function parameters and frequency of replacement fibrosis. No patient had cirrhosis/fibrosis, diabetes or heart failure, and the frequency of endocrinopathies was comparable among the groups. In pediatric beta-TDT patients, there is an association between genotype and cardiac and pancreatic iron overload. The knowledge of patients' genotype can be valuable in predicting some patients' phenotypic features and in helping the clinical management of beta-TDT patients.