title: Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassaemia.
abstract: The incidence of endocrine dysfunction in relation to the detailed genotype of beta-thalassaemia is investigated in this study. In addition, the association of genotype to specific clinical features of beta-thalassaemia is examined, together with the relationship between serum ferritin levels and endocrine complications. Ninety-seven patients were included, all with transfusion dependent beta-thalassaemia. Patients were divided into 2 categories; group 1 consisted of patients with a beta0/beta0 genotype with or without a concomitant alpha-globin gene deletion as well as patients with beta0/beta+ or beta+/beta+ genotype and normal alpha-globin chain synthesis. Group 2 included patients with beta+/beta+ or beta+/beta0 genotype and one alpha-globin chain deletion and those with a moderate amount of beta-globin chain synthesis (beta++) and normal alpha-globin chain synthesis. The results showed that group 1 patients were more likely to have severe clinical disease (p=0.005). Sixty-four patients (66%) had at least 1 endocrine disorder and 39 (40%) had multiple endocrinopathies; the most common abnormality was hypogonadotrophic hypogonadism (HH). There was a significant association between patients with group 1 genotypes and the presence of HH and impaired glucose tolerance or diabetes. A positive correlation was demonstrated between serum ferritin concentrations and the presence of thyroid or parathyroid dysfunction.
authors.affiliation: Department of Obstetrics and Gynaecology, The Whittington Hospital, London, UK.
authors.forename: C E
authors.initials: CE
authors.lastname: Jensen
authors.forename: S M
authors.initials: SM
authors.lastname: Tuck
authors.forename: J
authors.initials: J
authors.lastname: Old
authors.forename: R W
authors.initials: RW
authors.lastname: Morris
authors.forename: A
authors.initials: A
authors.lastname: Yardumian
authors.forename: V
authors.initials: V
authors.lastname: De Sanctis
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
authors.forename: B
authors.initials: B
authors.lastname: Wonke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003676:Deferoxamine / Q000627:therapeutic use; D004700:Endocrine System Diseases / Q000150:complications*; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000150:complications; D019190:Iron Overload / Q000378:metabolism*; D008297:Male; D013997:Time Factors; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*
chemical_list: D005914:Globins; D003676:Deferoxamine