Beta thalassemia syndromes are among the most common monogenic disorders that occur globally and are generally inherited as autosomal recessive diseases. The beta globin gene HBB is found on the short arm of chromosome 11, and to date, more than 200 pathogenic HBB mutations have been identified. Beta globin and alpha globin combine to create the adult hemoglobin tetramer, which comprises 2 chains of each; however, reduced or absent synthesis of beta globin chains can create an imbalance that leads to accumulation and precipitation of free alpha chains in the red blood cell precursors. The result is anemia, which then stimulates erythropoietin synthesis that results in intense proliferation of bone marrow, skeletal deformities, dysregulated iron homeostasis, and increased levels of reactive oxygen species in the erythroid cells. Based on the severity of the phenotype, beta thalassemias are classified as either transfusion-dependent (TDT) or nontransfusion-dependent (NTDT).
Advances in understanding the pathophysiology of beta thalassemia have substantially improved patient management and led to a robust increase in life expectancy. However, longer survival brings its own set of issues. Moreover, the underlying pathophysiology of the syndromes has not been eliminated, and current treatments, although effective, are associated with complications. Improvements in survival have also been associated with age-related disorders that occur in the general population.
In a review article published in Expert Review of Hematology, Irene Motta, MD, of the department of clinical sciences and community health at the Università degli Studi di Milano in Italy, and colleagues discussed the management of common complications that have been observed in patients with beta thalassemia.
Cardiovascular diseases remain a significant cause of morbidity and the primary cause of death in patients with both TDT and NTDT. More than 70% of deaths in this patient population are due to cardiovascular disease, and arrhythmias are becoming more prevalent in adults who have experienced previous iron overload.
“All patients transitioned to adult care are monitored closely for these complications,” said Hayley Merkeley, MD, MSc, FRCPC, of the division of hematology at the University of British Columbia in Canada. “With respect to cardiac concerns, patients receive echocardiograms every 1 to 5 years depending on their symptoms, as well as a cardiac [magnetic resonance imaging scan] every 6 [to] 12 months.”
Arrhythmias should be treated as in the general population. Although ablation strategies can be considered in select cases, there are currently no specific recommendations for it.
Adrenal insufficiency is another complication of thalassemia, although the researchers noted that among all of the thalassemia-related endocrinopathies, adrenal insufficiency in particular has been poorly studied and underreported in adult patients. Because it tends to develop gradually over time, and symptoms may be nonspecific and attributed to chronic anemia, undetected adrenal insufficiency may eventually present as a life-threatening acute crisis.
It is recommended, therefore, that the annual endocrinological evaluation for patients with both TDT and NTDT who are older than 18 years should always include basal adrenal function evaluation (adrenocorticotropic hormone [ACTH] and cortisol basal levels), and replacement therapy with cortisone acetate should be given if a diagnosis of adrenal insufficiency is made. For patients with low or borderline basal cortisol levels, an ACTH stimulation test should be performed in order to identify adrenal insufficiency.