{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:56:55Z","timestamp":1760151415401,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bayer (Italy)","award":["na"],"award-info":[{"award-number":["na"]}]},{"DOI":"10.13039\/100007560","name":"Chiesi (Italy)","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent \u03b2-thalassemia (\u03b2-TDT). We considered 68 \u03b2-TDT patients (11.98 \u00b1 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network. Iron overload was quantified by T2* technique and biventricular function by cine images. Replacement myocardial fibrosis was evaluated by late gadolinium enhancement technique. Three groups of patients were identified: homozygous \u03b2+ (N = 19), compound heterozygous \u03b20\u03b2+ (N = 24), and homozygous \u03b20 (N = 25). The homozygous \u03b20 group showed significantly lower global heart and pancreas T2* values than the homozygous \u03b2+ group. Compared to patients with homozygous \u03b2+ genotype, \u03b20\u03b2+ as well as \u03b20\u03b20 patients were more likely to have pancreatic iron overload (odds ratio = 6.53 and 10.08, respectively). No difference was detected in biventricular function parameters and frequency of replacement fibrosis. No patient had cirrhosis\/fibrosis, diabetes or heart failure, and the frequency of endocrinopathies was comparable among the groups. In pediatric \u03b2-TDT patients, there is an association between genotype and cardiac and pancreatic iron overload. The knowledge of patients\u2019 genotype can be valuable in predicting some patients\u2019 phenotypic features and in helping the clinical management of \u03b2-TDT patients.<\/jats:p>","DOI":"10.3390\/jpm12030400","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:38:16Z","timestamp":1646599096000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-8585","authenticated-orcid":false,"given":"Antonella","family":"Meloni","sequence":"first","affiliation":[{"name":"Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"},{"name":"U.O.C. Bioingegneria, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-2769","authenticated-orcid":false,"given":"Laura","family":"Pistoia","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-3308","authenticated-orcid":false,"given":"Paolo","family":"Ricchi","sequence":"additional","affiliation":[{"name":"U.O.S.D. Malattie Rare del Globulo Rosso, Azienda Ospedaliera di Rilievo Nazionale \u201cA. Cardarelli\u201d, 80131 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Caterina","family":"Putti","sequence":"additional","affiliation":[{"name":"Dipartimento della Salute della Donna e del Bambino, Clinica di Emato-Oncologia Pediatrica, Azienda Ospedaliero-Universit\u00e0 di Padova, 35128 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rita","family":"Gamberini","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Day Hospital della Talassemia e delle Emoglobinopatie, Dipartimento della Riproduzione e dell\u2019Accrescimento, Azienda Ospedaliero-Universitaria \u201cS. Anna\u201d, 44124 Cona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liana","family":"Cuccia","sequence":"additional","affiliation":[{"name":"U.O.C. Ematologia con Talassemia, ARNAS Civico \u201cBenfratelli-Di Cristina\u201d, 90134 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Messina","sequence":"additional","affiliation":[{"name":"Centro Microcitemie, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89100 Reggio Calabria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Massei","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Oncoematologia Pediatrica, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Facchini","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa di Pediatria\u2014Prof A Pession Programma di Oncologia, Ematologia e Trapianto Azienda Ospedaliero-Universitaria di Bologna\u2014Policlinico \u201cS. Orsola-Malpighi\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Righi","sequence":"additional","affiliation":[{"name":"Diagnostica per Immagini e Radiologia Interventistica, Ospedale del Delta, 44023 Lagosanto, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Renne","sequence":"additional","affiliation":[{"name":"Struttura Complessa di Cardiologia-UTIC, Presidio Ospedaliero \u201cGiovanni Paolo II\u201d, 88046 Lamezia Terme, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Peritore","sequence":"additional","affiliation":[{"name":"U.O.C. di Radiologia, ARNAS Civico \u201cBenfratelli-Di Cristina\u201d, 90134 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-9572","authenticated-orcid":false,"given":"Vincenzo","family":"Positano","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"},{"name":"U.O.C. Bioingegneria, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0579-3279","authenticated-orcid":false,"given":"Filippo","family":"Cademartiri","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1097\/GIM.0b013e3181cd68ed","article-title":"Beta-thalassemia","volume":"12","author":"Cao","year":"2010","journal-title":"Genet. Med."},{"key":"ref_2","first-page":"649","article-title":"Genetic modifiers of beta-thalassemia","volume":"90","author":"Thein","year":"2005","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1182\/blood-2010-01-251348","article-title":"The inherited diseases of hemoglobin are an emerging global health burden","volume":"115","author":"Weatherall","year":"2010","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00062752-200203000-00007","article-title":"Pathophysiology of thalassemia","volume":"9","author":"Schrier","year":"2002","journal-title":"Cur.r Opin. Hematol."},{"key":"ref_5","unstructured":"Cappellini, M.D., Cohen, A., Porter, J., Taher, A., and Viprakasit, V. (2014). Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT), Thalassaemia International Federation. [3rd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1056\/NEJM200004273421716","article-title":"Disorders of iron metabolism","volume":"342","author":"Andrews","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbagen.2008.09.010","article-title":"Iron overload following red blood cell transfusion and its impact on disease severity","volume":"1790","author":"Ozment","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(04)00343-5","article-title":"Balancing acts: Molecular control of mammalian iron metabolism","volume":"117","author":"Hentze","year":"2004","journal-title":"Cell"},{"key":"ref_9","first-page":"1187","article-title":"Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine","volume":"89","author":"Rugolotto","year":"2004","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1007\/s00330-007-0683-1","article-title":"Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: A T2 relaxometry study","volume":"17","author":"Argyropoulou","year":"2007","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1532-429X-15-1","article-title":"Cardiac and hepatic iron and ejection fraction in thalassemia major: Multicentre prospective comparison of combined deferiprone and deferoxamine therapy against deferiprone or deferoxamine monotherapy","volume":"15","author":"Pepe","year":"2013","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1532-429X-10-42","article-title":"Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance","volume":"10","author":"Modell","year":"2008","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pepe, A., Pistoia, L., Gamberini, M.R., Cuccia, L., Lisi, R., Cecinati, V., Maggio, A., Sorrentino, F., Filosa, A., and Rosso, R. (2021). National networking in rare diseases and reduction of cardiac burden in thalassemia major. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehab851"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"728","DOI":"10.3892\/br.2016.646","article-title":"Impact of genotype on endocrinal complications in beta-thalassemia patients","volume":"4","author":"Badr","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcmd.2019.01.008","article-title":"Cardiac involvement by CMR in different genotypic groups of thalassemia major patients","volume":"77","author":"Pistoia","year":"2019","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s12288-018-1034-x","article-title":"Impact of Genotype of Beta Globin Gene on Hepatic and Myocardial Iron Content in Egyptian Patients with Beta Thalassemia","volume":"35","author":"Hassan","year":"2019","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/jmri.21781","article-title":"Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron","volume":"30","author":"Ramazzotti","year":"2009","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1007\/s00330-018-5783-6","article-title":"Multicenter validation of the magnetic resonance T2* technique for quantification of pancreatic iron","volume":"29","author":"Meloni","year":"2019","journal-title":"Eur. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ijmedinf.2009.02.011","article-title":"Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia","volume":"78","author":"Meloni","year":"2009","journal-title":"Int. J. Med. Inf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.mri.2008.06.004","article-title":"Improved T2* assessment in liver iron overload by magnetic resonance imaging","volume":"27","author":"Positano","year":"2009","journal-title":"Magn. Reson. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/mrm.22640","article-title":"Regional and global pancreatic T*(2) MRI for iron overload assessment in a large cohort of healthy subjects: Normal values and correlation with age and gender","volume":"65","author":"Restaino","year":"2011","journal-title":"Magn. Reson. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/ehjci\/jeu191","article-title":"Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy","volume":"16","author":"Meloni","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/mrm.22410","article-title":"Preferential patterns of myocardial iron overload by multislice multiecho T*2 CMR in thalassemia major patients","volume":"64","author":"Meloni","year":"2010","journal-title":"Magn. Reson. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1002\/nbm.1121","article-title":"Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts","volume":"20","author":"Positano","year":"2007","journal-title":"NMR Biomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/jmri.22417","article-title":"Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload","volume":"33","author":"Meloni","year":"2011","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1111\/bjh.12296","article-title":"The use of appropriate calibration curves corrects for systematic differences in liver R2* values measured using different software packages","volume":"161","author":"Meloni","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1182\/blood-2004-10-3982","article-title":"MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients","volume":"106","author":"Wood","year":"2005","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1007\/s00261-015-0522-9","article-title":"Accurate estimate of pancreatic T2* values: How to deal with fat infiltration","volume":"40","author":"Meloni","year":"2015","journal-title":"Abdom. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1161\/hc0402.102975","article-title":"Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association","volume":"105","author":"Cerqueira","year":"2002","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/jmri.27169","article-title":"Biventricular Reference Values by Body Surface Area, Age, and Gender in a Large Cohort of Well-Treated Thalassemia Major Patients without Heart Damage Using a Multiparametric CMR Approach","volume":"53","author":"Meloni","year":"2021","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3324\/haematol.2010.025510","article-title":"Cardiac iron and cardiac disease in males and females with transfusion-dependent thalassemia major: A T2* magnetic resonance imaging study","volume":"96","author":"Marsella","year":"2011","journal-title":"Haematologica"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.3324\/haematol.2009.010181","article-title":"Safety of cardiovascular magnetic resonance gadolinium chelates contrast agents in patients with hemoglobinopaties","volume":"94","author":"Meloni","year":"2009","journal-title":"Haematologica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2459\/JCM.0000000000000278","article-title":"Myocardial fibrosis by late gadolinium enhancement cardiac magnetic resonance and hepatitis C virus infection in thalassemia major patients","volume":"16","author":"Pepe","year":"2015","journal-title":"J. Cardiovasc. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJM200008033430503","article-title":"Hepatic iron concentration and total body iron stores in thalassemia major","volume":"343","author":"Angelucci","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1053\/euhj.2001.2822","article-title":"Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload","volume":"22","author":"Anderson","year":"2001","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1161\/CIRCULATIONAHA.110.007641","article-title":"On T2* magnetic resonance and cardiac iron","volume":"123","author":"Carpenter","year":"2011","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2016058","DOI":"10.4084\/mjhid.2016.058","article-title":"The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients","volume":"8","author":"Soliman","year":"2016","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4103\/2230-8210.107808","article-title":"Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines","volume":"17","author":"Soliman","year":"2013","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2019029","DOI":"10.4084\/mjhid.2019.029","article-title":"Thyroid Disorders in Homozygous beta-Thalassemia: Current Knowledge, Emerging Issues and Open Problems","volume":"11","author":"Soliman","year":"2019","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/MED.0b013e3283591502","article-title":"Hypoparathyroidism: From diagnosis to treatment","volume":"19","author":"Soliman","year":"2012","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_42","first-page":"79","article-title":"Growth hormone deficiency in adults with thalassemia: An overview and the I-CET recommendations","volume":"222","author":"Soliman","year":"2013","journal-title":"Georgian Med. News"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1161\/CIRCULATIONAHA.109.192064","article-title":"2009 focused update: ACCF\/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines: Developed in collaboration with the International Society for Heart and Lung Transplantation","volume":"119","author":"Jessup","year":"2009","journal-title":"Circulation"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1161\/CIRCULATIONAHA.106.180199","article-title":"ACC\/AHA\/HRS 2006 key data elements and definitions for electrophysiological studies and procedures: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Data Standards (ACC\/AHA\/HRS Writing Committee to Develop Data Standards on Electrophysiology)","volume":"114","author":"Buxton","year":"2006","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1182\/blood-2018-06-818187","article-title":"How I manage medical complications of beta-thalassemia in adults","volume":"132","author":"Taher","year":"2018","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1093\/ehjci\/jex012","article-title":"Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: A prospective multicentre study by a multi-parametric approach","volume":"19","author":"Pepe","year":"2018","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1046\/j.1365-2257.2001.00367.x","article-title":"Molecular analysis of beta-thalassaemia patients in a high incidence area of southern Italy","volume":"23","author":"Rigoli","year":"2001","journal-title":"Clin. Lab. Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s00277-020-04047-w","article-title":"Red blood cell consumption in a large cohort of patients with thalassaemia: A retrospective analysis of main predictors","volume":"99","author":"Ricchi","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1600-0609.2006.00681.x","article-title":"The impact of genotype on endocrine complications in thalassaemia major","volume":"77","author":"Skordis","year":"2006","journal-title":"Eur. J. Haematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1182\/blood-2008-04-148767","article-title":"Longitudinal analysis of heart and liver iron in thalassemia major","volume":"112","author":"Noetzli","year":"2008","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ajh.23405","article-title":"Treating iron overload in patients with non-transfusion-dependent thalassemia","volume":"88","author":"Taher","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_52","first-page":"64","article-title":"Iron Overload and Iron Chelation Therapy in Pediatric Patients","volume":"2","author":"Vichinsky","year":"2009","journal-title":"Oral. Hist. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.2337\/dc20-0908","article-title":"The Close Link of Pancreatic Iron with Glucose Metabolism and with Cardiac Complications in Thalassemia Major: A Large, Multicenter Observational Study","volume":"43","author":"Pepe","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.3324\/haematol.2017.170605","article-title":"Residual erythropoiesis protects against myocardial hemosiderosis in transfusion-dependent thalassemia by lowering labile plasma iron via transient generation of apotransferrin","volume":"102","author":"Garbowski","year":"2017","journal-title":"Haematologica"},{"key":"ref_55","first-page":"538","article-title":"Soluble form of transferrin receptor as a biomarker of overall morbidity in patients with non-transfusion-dependent thalassaemia: A cross-sectional study","volume":"14","author":"Ricchi","year":"2016","journal-title":"Blood Transfus."},{"key":"ref_56","first-page":"s124","article-title":"Extramedullary haematopoiesis correlates with genotype and absence of cardiac iron overload in polytransfused adults with thalassaemia","volume":"12","author":"Ricchi","year":"2014","journal-title":"Blood Transfus."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/ajh.24139","article-title":"Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients","volume":"90","author":"Ricchi","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"5-Noetzli, L.J., Mittelman, S.D., Watanabe, R.M., Coates, T.D., and Wood, J.C. (2012). Pancreatic iron and glucose dysregulation in thalassemia major. Am. J. Hematol., 87, 155\u2013160.","DOI":"10.1002\/ajh.22223"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1182\/blood-2009-06-225615","article-title":"Pancreatic iron loading predicts cardiac iron loading in thalassemia major","volume":"114","author":"Noetzli","year":"2009","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"E189","DOI":"10.1002\/ajh.24081","article-title":"Pancreatic iron overload by T2* MRI in a large cohort of well treated thalassemia major patients: Can it tell us heart iron distribution and function?","volume":"90","author":"Meloni","year":"2015","journal-title":"Am. J. Hematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.12688\/f1000research.25943.1","article-title":"The relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions, hepatic and cardiac iron siderosis among Egyptian children and young adults with beta-thalassaemia major and sickle cell disease: A cross-sectional study","volume":"9","author":"Salama","year":"2020","journal-title":"F1000Research"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/j.1600-0609.2011.01662.x","article-title":"Importance of optimal dosing >\/= 30 mg\/kg\/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with beta-thalassaemia","volume":"87","author":"Taher","year":"2011","journal-title":"Eur. J. Haematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1600-0609.1997.tb00729.x","article-title":"Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassaemia","volume":"59","author":"Jensen","year":"1997","journal-title":"Eur. J. Haematol."},{"key":"ref_64","first-page":"642","article-title":"Endocrine complications in patients with Thalassaemia Major","volume":"5","author":"Toumba","year":"2007","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/bjh.12557","article-title":"Cardiac complications and diabetes in thalassaemia major: A large historical multicentre study","volume":"163","author":"Pepe","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13052-021-01116-2","article-title":"Detection of endocrine disorders in young children with multi-transfused thalassemia major","volume":"47","author":"Mahmoud","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/08880018.2020.1734124","article-title":"The effect of deferasirox on endocrine complications in children with thalassemia","volume":"37","author":"Bilgin","year":"2020","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1097\/00043426-200311000-00011","article-title":"Hypogonadotropic hypogonadism and hematologic phenotype in patients with transfusion-dependent beta-thalassemia","volume":"25","author":"Chern","year":"2003","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_69","first-page":"168","article-title":"Genotypic groups as risk factors for cardiac magnetic resonance abnormalities and complications in thalassemia major: A large, multicentre study","volume":"19","author":"Pistoia","year":"2021","journal-title":"Blood Transfus."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/3\/400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:32:23Z","timestamp":1760135543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/3\/400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,4]]},"references-count":69,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jpm12030400"],"URL":"https:\/\/doi.org\/10.3390\/jpm12030400","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2022,3,4]]}}}