The Link of Pancreatic Iron with Glucose Metabolism and Cardiac Iron in Thalassemia Intermedia: A Large, Multicenter Observational Study

In thalassemia major, pancreatic iron was demonstrated as a powerful predictor not only for the alterations of glucose metabolism but also for cardiac iron, fibrosis, and complications, supporting a profound link between pancreatic iron and heart disease. We determined for the first time the prevalence of pancreatic iron overload (IO) in thalassemia intermedia (TI) and systematically explored the link between pancreas T2* values and glucose metabolism and cardiac outcomes. We considered 221 beta-TI patients (53.2% females, 42.95 ± 13.74 years) consecutively enrolled in the Extension–Myocardial Iron Overload in Thalassemia project. Magnetic Resonance Imaging was used to quantify IO (T2* technique) and biventricular function and to detect replacement myocardial fibrosis. The glucose metabolism was assessed by the oral glucose tolerance test (OGTT). Pancreatic IO was more frequent in regularly transfused (N = 145) than in nontransfused patients (67.6% vs. 31.6%; p < 0.0001). In the regular transfused group, splenectomy and hepatitis C virus infection were both associated with high pancreatic siderosis. Patients with normal glucose metabolism showed significantly higher global pancreas T2* values than patients with altered OGTT. A pancreas T2* < 17.9 ms predicted an abnormal OGTT. A normal pancreas T2* value showed a 100% negative predictive value for cardiac iron. Pancreas T2* values were not associated to biventricular function, replacement myocardial fibrosis, or cardiac complications. Our findings suggest that in the presence of pancreatic IO, it would be prudent to initiate or intensify iron chelation therapy to prospectively prevent both disturbances of glucose metabolism and cardiac iron accumulation.

Compound heterozygous delta beta thalassemia with IVS 1-5 (G>C) mutation presenting as thalassemia major phenotype

Delta beta thalassemia is an unusual variant of thalassemia with elevated level of fetal hemoglobin (HbF). Unlike beta thalassemia, delta beta thalassemia heterozygotes have milder phenotype and homozygotes present as thalassemia intermedia phenotype. We report a 11-month-old male child who presented with severe anemia, and hepatosplenomegaly, thalassemia major phenotype. On evaluation was diagnosed as compound heterozygous for δβ0/β thalassemia with IVS 1-5 (G>C) mutation. This case highlights the importance of genotyping of patients with δβ thalassemia and co-inheritance of δβ thalassemia deletion with point mutation for β-thalassemia results in severe clinical phenotype as thalassemia major.

Study Tanner staging of β- thalassemic patients attending thalassemic Center in Ibn Al-Atheer Teaching Pediatric Hospital

Purpose: determine any relationship between tanner staging of the patients and transfusion program, iron overload and chelation therapy and study tanner staging of β- thalassemic patients attending Thalassemic Center in Ibn Al-Atheer Teaching Pediatric Hospital. Patients and Methods: A descriptive-analytic study (case series study) was done on β- thalassemic patients attending Thalassemia Center in Ibn Al- Atheer Teaching Hospital in Mosul, during the period from the 1st of January to the 30th of June 2019.Sixty patients with β- thalassemia, 45 of them are β- thalassemia major cases and 15 are β- thalassemia intermedia cases. The patients of the major type were sub-classified into 3 groups according to their ages: Group 1, Patients from the age of ≥ 13 years; Group 2, Patients from the age of 14 years to 16 years and Group 3, Patients from the age of more than 17 years. Results: current study showed male (77.78, 66.67) % more than female (22.22; 33.33) % in both types of thalassemia (Major and Intermedia) respectively.so the most of the patients in this study live in urban areas (58.33%) and (41.67%) in rural areas, mean age at diagnosis of thalassemia major was 7.16 months, Delayed tanner staging was found in 64.44% of patients with thalassemia major, while in thalassemia intermedia only 33.33% were considered to be on a delayed stage. as well as 4(80%) of Tanner Stage (II) for pateints in age group (≥ 13) years compare to 20% for stage (III), so 50% for both stage (II and III) respectively in age group (14-16) years. Conclusion: Two-third of the patients with thalassemia major had delayed puberty (64.44%), while one- third of the patients with thalassemia intermedia had delayed pubertal development (33.33%).

Beta-thalassemia intermedia with ischemic transients misdiagnosed as multiple sclerosis: A case report

The article's abstract is not available.

EXPRESS: Murine models of sickle cell disease and beta-thalassemia demonstrate pulmonary hypertension with distinctive features.

Sickle cell anemia (SCA) and β-thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension (PH). The etiologies responsible for the associated development of PH in both diseases are multi-factorial with extensive mechanistic contributors described. Both SCA and β-thalassemia intermedia present with intra and extravascular hemolysis, and because SCA and β-thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the PH phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of SCA PH patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study we hypothesized that a common pathophysiology would characterize the PH phenotype in SCA and β-thalassemia intermedia murine models, but because unlike SCA, β-thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, there may be differences as well. Herein we describe common and divergent features of PH in aged Berk-ss (SCA) and Hbbth/3+ (intermediate β-thalassemia) mice and suggest translational utility as proof-of-concept models to study PH therapeutics specific to genetic anemias.

Endothelial dysfunction in patients with hereditary spherocytosis and b-thalassemia

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

The Molecular Basis of Beta-Thalassemia Intermedia in Egyptian Children and its Association with the Clinical Phenotype

Background β-thalassemia syndromes involve a collection of extremely diverse phenotypes. The term β-thalassemia intermedia (β-TI) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor thalassemia yet too mild to be termed major thalassemia. However, there remains substantial overlap between the three conditions. Aim of the Work To evaluate the variable clinical phenotypes among pediatric patients with βTI and to study the phenotype / genotype correlation with the encountered β-chain mutations. Patients and Methods A cross-sectional study was conducted on 37 Egyptian children and adolescents with TI following up regularly in the Pediatric Hematology clinic – Ain Shams University. Detailed Clinical evaluation and laboratory investigations were done. Reverse hybridization PCR based assay covering beta globin Mediterranean mutations onto specific biotinylated primers, was done. Results IVS 1.6 (T&gt;C) was the most frequent mutation detected in 20 patients and 31 alleles (47.7%), followed by IVS 1.110 (G&gt;A) detected in 7 patients and 8 alleles (12.31%), followed by IVS 1.1 (G&gt;A) and CD27 knossos (G&gt;T), each was detected in 6 patients and 6 alleles (9.23%). β+β+ was the most frequent genotype (54%), followed by β+β/β°β (21.6%) and β°β+ (13.5%). 60% of β°β+ patients had TDT(Transfusion dependent thalassemia), while 87.5% of β + β/β°β patients and 55% of β + β+ patients had NTDT ((Non transfusion dependent thalassemia). Conclusion Inheritance of mild β+ thalassemia mutations among Egyptian children; as IVS 1.6 (T&gt;C) and IVS 1.110 (G&gt;A) is the most frequent contributor to TI phenotype in either homozygous or compound heterozygous states. Patients with the same underlying genotype presented variable phenotypes with different degrees of severity.