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Hb Adana is a highly unstable and rare α-globin hemoglobin (Hb) variant, to date described in only three families, in interaction with other α-thalassemia (α-thal) deletions. We describe the clinical and hematological findings in two cases from independent families of Albanian origin, who have an interaction of the codon 59 (Gly→Asp) α2-globin gene variant in trans to a 3.7 kb α+-thal deletion (αcodon 59α/-α). We report their presenting symptoms and laboratory findings as well as complications and differences in their clinical management. Both cases can be characterized as thalassemia intermedia and illustrate the problems associated with selecting the most appropriate options for patient management, especially in cases with rare underlying genotypes. [ABSTRACT FROM AUTHOR]

Despite intense iron-chelation therapy, the life expectancy of patients with beta-thalassemia major (beta-TM) is still limited by the occurrence of heart failure. In the present study, we sought to evaluate the prognostic significance of several clinical factors on the outcome of heart failure or arrhythmias in patients with beta-TM. The study group consisted of 131 consecutive young patients with beta-TM (71 men aged 21+/-4 years, 60 women aged 22+/-5 years) who were initially examined during 1995. The clinical and vital statuses of all patients were biannually reviewed from 1995 to 2004. Cox proportional hazards models were used to evaluate the association of the occurrence of death or nonfatal events due to heart failure or arrhythmias with clinical factors (systolic and diastolic blood pressures), echocardiographic factors (left and right ventricular diameters, left atrial and aortic root dimensions, left ventricular ejection fraction), electrocardiographic factors (T-wave inversion in leads V1-V3, QRS duration, heart rate), and serum ferritin levels, after controlling for age, sex, and body mass index. During the follow-up, 11 men (16%) and 5 women (8%) had an event (men versus women, P = .212). The age-adjusted event rate was 16 events per 913 person-years (2%). The presence of T-wave inversion in right precordial leads (hazard ratio = 3.06; 95% confidence interval [CI], 1.1-8.8), increased heart rate (hazard ratio = 1.28; 95% CI, 1.03-1.58), decreased aortic root diameter (hazard ratio = 0.84; 95% CI, 0.73-0.96), and decreased ejection fraction (hazard ratio per 1% change = 0.95; 95% CI, 0.91-0.99) were associated with a higher risk for a cardiac event. We revealed that the presence of T-wave inversions, increased heart rate, low ejection fraction of the left ventricle, and decreased aortic root diameter appear to confer higher risk for cardiac events in young patients with beta-TM. [ABSTRACT FROM AUTHOR]

Background and Aim: Dysregulation of glucose metabolism is a common complication of transfusions in Transfusion Dependent Thalassemia (TDT) patients. For early diagnosis of glucose disturbances, screening is recommended. The age of starting and the type of screening vary; the more common methods are assessment of RPG, FPG, 2h PG and 2 hours OGTT. The combined assessment of glucose tolerance and insulin response during OGTT is rarely recommended. The main objective of the study is the evaluation of simultaneous assessment of Glucose Tolerance (GT) and Insulin Response (IR) during OGTT in patients with TDT., Methods: 43 TDT patients aged 12-28years, without clinical evidence of glucose disturbances, were randomly selected for the study. The 2-hour OGTT in 30 minutes intervals was applied. Plasma glucose and insulin were assessed in all samples using routine laboratory methods., Results: Of 43 patients 31(72%) had Normal GT; of them 9 (29%) had normal insulin response  (NIR), 14 (45%) high IR and 8(26%) delayed peak IR. Delayed peak IR was found in 8 of the 9 patients with Impaired GT and in 2 of the 3 with diabetic GT. Deficient IR (hypoinsulinemia) was found in two patients., Conclusions: Simultaneous assessment of GT and IR during OGTT in TDT patients, seems to be a most sensitive and creditable screening test for early diagnosis of glucose disturbances. High IR and delayed peak IR in normoglycemic patients are valuable indices for diagnosis of the pre-diabetic state that precede the development of glucose disturbances in TDT patients and start proper follow and management.

Background: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family., Aims of the Study: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies., Results: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with β- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions"., Conclusions: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.

In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the  reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of  physicians' current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended.

Background: Bone changes are a prominent symptom of beta-thalassemias, related to expansion of bone marrow and reduction of bone density. Conventional treatment ameliorates bone changes and improves survival, thus increasing the morbidity of bone diseases in adulthood. Peripheral quantitative computer tomography (pQCT) was used recently to assess the changes in volumetric bone mineral density (vBMD) in various bone compartments., Objectives: Assessment of indices of bone density and structure in patients with thalassemia major (thal-major) and intermedia (thal-interm) on conventional therapy and in healthy adults., Material and Methods: 45 patients with thal-major, 27 with thal-interm and 32 healthy individuals aged 21-42 years were studied by pQCT analysis. The vBMD total (tot), trabecular (trab) and cortical (cort), the bone mineral content (BMC), the cross sectional area (CSA), the cortical thickness (CRTHK) and the stress strain index (SSI) were assessed at the 4% site of the distal radius., Results: Tot, trab, and cort vBMD, BMC, and cortical thickness showed statistically significant differences among the three groups with significant reduction in thalassemics. No significant differences were found in the three groups with CSA and SSI. Impairment of bone density and structure in Greek thalassemics on proper treatment was not as severe as expected. A significant proportion of patients had bone density indices within the normal range and above the 10th percentile of normal., Conclusions: Peripheral QCT analysis is a convenient method to study the regional changes of bone density in patients with thalassemia. These changes affect mainly the cortical compartment and are more pronounced in thalassemia intermedia.

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.

Background: Expansion of marrow spaces in thalassemia patients contributes to reduced bone density and increased risk of fractures. Peripheral quantitative computed tomography (pQCT) measures the volumetric bone mineral density (vBMD) independently in different compartments., Objective and Methods: To study the regional bone structure in thalassemia, we performed pQCT (XCT-2000 Scanner, Stratec Inc.) in 57 young adult patients with beta-thalassemia major, aged 21-44 years (32 females). The vBMDs (total, trabecular, cortical + subcortical), Stress-Strain Index (SSI) and the cross-sectional area (CSA) were determined at the "4% site" of the distal radius; data were compared to reference values., Results: Total vBMD, trabecular, cortical plus subcortical vBMD in thalassemics were significantly lower than in healthy adults (p<0.005). Thalassemic males had significant higher values of vBMD, SSI and CSA than females (p<0.005)., Conclusions: In Greek thalassemic patients a significant reduction in bone density, associated with increased morbidity and risk of fractures, has been detected on pQCT examination.

Objective: To study the evolution of glucose disturbances (GD) in patients with thalassemia aged 11-30 years., Design and Methods: A total of 263 patients, classified into three groups on the basis of age, and period of follow-up ranging from 2-10 years, were studied. Evolution of GD was assessed through serial oral glucose tolerance tests (OGTT), based on WHO criteria., Results: At baseline (11-14 years of age) evaluation of OGTT disclosed a prevalence of 16.3% of impaired glucose tolerance (IGT), and zero for diabetic tolerance (DT). Prevalence of IGT increased progressively up to 39% in the following 4 years, but remained constant during the last 6 years of observation. In contrast, DT had a very low prevalence, beginning with 0.5% at 13-16 years, increasing to 2.4% by the age of 21-24 years., Conclusions: During puberty and early adolescence impaired glucose tolerance (IGT) was found in a considerable proportion of thalassemics. In contrast, DT was infrequent and progression to DM was slow. Only 12.4% of patients with IGT developed DT within a period of 10 years. Further studies are necessary to identify all of the factors contributing to abnormalities of glucose metabolism in thalassemic patients.