Impact of genotype on endocrinal complications in β-thalassemia patients

Abstract

In β-thalassemia, certain mutations cause a complete absence of β-globin chain synthesis, termed β-thalassemia, while others may allow certain β-globin production and are termed β- or β-thalassemia. The homozygous state results in severe anemia, which requires regular blood transfusion. By contrast, frequent blood transfusion can in turn lead to iron overload, which may result in several endocrinal complications. The present study aimed to investigate the impact of genotype on the development of endocrine complications in β-thalassemia patients. A cross-sectional study was conducted on 100 thalassemia patients >10 years. A data abstraction form was designed to capture the appropriate information from the individual medical records, including full clinical, laboratory, transfusion and chelation data. The genotype of the patients was identified by the DNA sequencing technique. Growth retardation and hypogonadism were the most prominent endocrinal complications (70 and 67%, respectively) followed by hypothyroidism, diabetes mellitus and hypoparathyrodism (8, 8 and 7%, respectively). The most common mutations identified were IVS-1-110, IVS-1-1 and IVS-1-6 (63, 47 and 41%, respectively). Patients with the ββ genotype had a significantly higher prevalence of growth retardation, hypogonadism, hypothyroidism and hypoparathyrodism compared to those with the ββ and ββ genotypes (P<0.001, P<0.001, P<0.001 and P=0.037, respectively). Patients with the homozygous IVS-11-745 mutation had a significantly higher prevalence of diabetes (P=0.001). The underlying genetic defect in thalassemia patients is a contributing factor for the development of endocrinal complications, as patients with the more severe defects have a greater rate of iron loading through higher red cell consumption.

Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients withβ-Thalassemia Major: A Meta-Analysis

“…Two studies [6, 7] were excluded due to the duplicated publication. Finally, of 51 full-text articles, only 42 studies were included in this meta-analysis [2–5, 8–45]. In addition, two studies were identified from reference lists [46, 47].…”

“…The selection flow chart is shown in Figure 1. Of the included studies, seven studies [30, 33, 34, 36, 39, 40, 43] were from Italy; seven studies [14, 16, 18, 20, 21, 31, 42] were from Iran; five studies [17, 19, 27, 44, 45] were from Egypt; five studies [4, 8, 22, 23, 35] were from the China region, including the mainland [22], Hong Kong [23], and Taiwan [4, 8, 35]; three studies [11, 12, 32] were from India; two studies [41, 47] were from Arabia; one study [37] was from Germany. The other studies were from Australia [26], Brazil [3], France [9], Lebanon [41], Oman [15], Turkey [25, 38], the United Kingdom [46], and the United States of America [2].…”

“…Eight studies [7, 14, 15, 19, 27, 29, 35, 39] reported the age at first diagnosis of abnormal glucose metabolism. 20 studies [2, 3, 9, 11, 12, 14, 15, 17, 19, 21–25, 27, 29, 35, 38, 41, 45] reported the serum ferritin level in β -thalassemia major patients. Baseline characteristics are listed in Table 1.…”

“…Baseline characteristics are listed in Table 1. As one of the most important indicators of endocrinopathy in β -thalassemia major, association between the serum ferritin levels and abnormal glucose metabolism was also determined based on 20 studies [2, 3, 9, 11, 12, 14, 15, 17, 19, 21–25, 27, 29, 35, 38, 41, 45]. When compared to normal glucose metabolism group, the mean serum ferritin level in abnormal glucose metabolism significant elevated (SMD=1.40, 95% CI: 0.44-2.36; Z=2.85, p=0.004).…”

Severe Liver Iron Concentrations (Lic) in 24 Patients With Β-Thalassemia Major: Correlations With Serum Ferritin, Liver Enzymes and Endocrine Complications

“…However, due to the multifactorial causes of endocrine disorders in BTM patients, other factors such as: duration and adherence to prescribed chelation regimens, transfusional iron burden and biological responsiveness to a given chelation regimen could play an additional role in determining the degree of iron overload and development of organs damage. 13 – 16 …”