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

Abstract

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 β-thalassemia (β-TDT). We considered 68 β-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 β+ (N = 19), compound heterozygous β0β+ (N = 24), and homozygous β0 (N = 25). The homozygous β0 group showed significantly lower global heart and pancreas T2* values than the homozygous β+ group. Compared to patients with homozygous β+ genotype, β0β+ as well as β0β0 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 β-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 β-TDT patients.

Keywords: complications; genotype; iron overload; transfusion-dependent thalassemia.

Figure 1

(A) Mean global pancreas T2* values in the three groups identified based on the β-globin gene phenotypic expression. (B) Frequency of patients with global pancreas T2* < 26 ms in the three phenotypic groups. The p-value for each significant pairwise comparison is indicated.

Figure 2

Mean global heart T2* values in the three groups identified based on the β-globin gene phenotypic expression. The p-value for each significant pairwise comparison is indicated.