β-Thalassemia intermedia: a comprehensive overview and novel approaches

Abstract

β-Thalassemia intermedia is a clinical condition of intermediate gravity between β-thalassemia minor, the asymptomatic carrier, and β-thalassemia major, the transfusion-dependent severe anemia. It is characterized by a significant clinical polymorphism, which is attributable to its genetic heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload contribute to the clinical complications of thalassemia intermedia through stepwise pathophysiological mechanisms. These complications, including splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers, thrombophilia, and bone abnormalities can be managed via fetal hemoglobin induction, occasional transfusions, chelation, and in some cases, stem cell transplantation. Given its clinical diversity, thalassemia intermedia patients require tailored approaches to therapy. Here we present an overview and novel approaches to the genetic basis, pathophysiological mechanisms, clinical complications, and optimal management of thalassemia intermedia.

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento.

“…Estas son causadas por daño del eje hipotalámico o daño directo del órgano final manifestándose como una falla de crecimiento, hipotiroidismo, hipoparatiroidismo, diabetes mellitus e hipogonadismo [49]. La prevalencia de endocrinopatías en β-Talasemia está directamente relacionada con el nivel de sobrecarga de hierro [50]. A pesar de la pubertad retrasada, estos pacientes todavía tienen un desarrollo sexual y fertilidad normales [50].…”

“…La prevalencia de endocrinopatías en β-Talasemia está directamente relacionada con el nivel de sobrecarga de hierro [50]. A pesar de la pubertad retrasada, estos pacientes todavía tienen un desarrollo sexual y fertilidad normales [50].…”

“…Esta condición puede desarrollarse a través de lesiones túbulo-intersticiales y / o glomerulares. La disfunción renal puede ocurrir en pacientes asintomáticos con TDT incluso antes de tener las manifestaciones de cualquier otra complicación [50]. Existen Varios factores principales que pueden ser responsables de la disfunción renal asociada con TDT, incluida la reducción de la vida de los glóbulos rojos, la hipoxia crónica, el rápido recambio de hierro y la deposición de exceso de hierro en los tejidos [51].…”

Thalassemia in the laboratory: pearls, pitfalls, and promises

“…These patients commonly have iron overload as a result of ineffective erythropoiesis or serial blood transfusions, and they exhibit increased serum iron and ferritin levels [52]. Excess iron is accumulated in organs, causing heart failure; portal and hepatocyte iron loading; and endocrine dysfunctions, such as diabetes, hypogonadism, thyroid dysfunction and growth retardation [53][54][55][56][57][58][59][60]. Therefore, evaluation of iron status, as well as the functionality of organs susceptible to iron accumulation, is part of the routine medical care of thalassemia patients [61,62].…”

Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening

“…The β -thalassemias can be grouped in different classes, depending on the β -globin gene mutations ( β 0 and β + -thalassemias) and on the transfusion dependency (transfusion-dependent and transfusion independent β -thalassemias). In the case of the most severe forms of β -thalassemia, regular blood transfusions and chelating therapies are the conventional therapeutic approaches [ 2 , 3 , 4 , 5 ]. While bone marrow transplantation is currently the only resolving treatment of the disease [ 6 ], several potentially curative strategies are under clinical validation, including gene therapy [ 7 ], gene editing [ 8 ], and treatment with novel agents potentiating hematopoiesis (i.e., luspatercept) [ 9 ].…”