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beta Thalassemia(BTHAL)

MedGen UID:
2611
Concept ID:
C0005283
Disease or Syndrome
Synonyms: BTHAL; Cooley's anemia; Erythroblastic anemia; Mediterranean anemia
SNOMED CT: beta thalassemia (65959000); Beta thalassemia (65959000); Beta thalassemia syndrome (65959000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): HBB (11p15.4); HBB-LCR (11p15.4)
 
Monarch Initiative: MONDO:0019402
OMIM®: 141900; 613985
Orphanet: ORPHA848

Authors:

Additional description

From MedlinePlus Genetics
In people with beta thalassemia, low levels of hemoglobin reduce oxygen levels in the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.

Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as transfusion-dependent thalassemia or Cooley's anemia) and thalassemia intermedia (which is a non-transfusion-dependent thalassemia). Of the two types, thalassemia major is more severe.

The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Puberty is delayed in some adolescents with thalassemia major. 

Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.

Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth, bone abnormalities, and an increased risk of developing abnormal blood clots.

Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.  https://medlineplus.gov/genetics/condition/beta-thalassemia

Clinical features

From HPO
Hypochromic microcytic anemia
MedGen UID:
124413
Concept ID:
C0271901
Disease or Syndrome
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
Reduced beta/alpha synthesis ratio
MedGen UID:
868732
Concept ID:
C4023137
Finding
A reduction in the ratio of production of beta globin to that of alpha globin. This is the major abnormality in the various forms of beta thalassemia.

Recent clinical studies

Etiology

Baird DC, Batten SH, Sparks SK
Am Fam Physician 2022 Mar 1;105(3):272-280. PMID: 35289581
Kattamis A, Forni GL, Aydinok Y, Viprakasit V
Eur J Haematol 2020 Dec;105(6):692-703. Epub 2020 Sep 21 doi: 10.1111/ejh.13512. PMID: 32886826Free PMC Article
Kohne E
Dtsch Arztebl Int 2011 Aug;108(31-32):532-40. Epub 2011 Aug 8 doi: 10.3238/arztebl.2011.0532. PMID: 21886666Free PMC Article
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Diagnosis

Ali S, Mumtaz S, Shakir HA, Khan M, Tahir HM, Mumtaz S, Mughal TA, Hassan A, Kazmi SAR, Sadia, Irfan M, Khan MA
Mol Genet Genomic Med 2021 Dec;9(12):e1788. Epub 2021 Nov 5 doi: 10.1002/mgg3.1788. PMID: 34738740Free PMC Article
Kattamis A, Forni GL, Aydinok Y, Viprakasit V
Eur J Haematol 2020 Dec;105(6):692-703. Epub 2020 Sep 21 doi: 10.1111/ejh.13512. PMID: 32886826Free PMC Article
Viprakasit V, Ekwattanakit S
Hematol Oncol Clin North Am 2018 Apr;32(2):193-211. doi: 10.1016/j.hoc.2017.11.006. PMID: 29458726
Origa R
Genet Med 2017 Jun;19(6):609-619. Epub 2016 Nov 3 doi: 10.1038/gim.2016.173. PMID: 27811859
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Therapy

Laurent M, Geoffroy M, Pavani G, Guiraud S
Cells 2024 May 8;13(10) doi: 10.3390/cells13100800. PMID: 38786024Free PMC Article
Locatelli F, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, de la Fuente J, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara M, Liem RI, Cappellini MD, Algeri M, Kattamis A, Sheth S, Grupp S, Handgretinger R, Kohli P, Shi D, Ross L, Bobruff Y, Simard C, Zhang L, Morrow PK, Hobbs WE, Frangoul H; CLIMB THAL-111 Study Group
N Engl J Med 2024 May 9;390(18):1663-1676. Epub 2024 Apr 24 doi: 10.1056/NEJMoa2309673. PMID: 38657265
Locatelli F, Thompson AA, Kwiatkowski JL, Porter JB, Thrasher AJ, Hongeng S, Sauer MG, Thuret I, Lal A, Algeri M, Schneiderman J, Olson TS, Carpenter B, Amrolia PJ, Anurathapan U, Schambach A, Chabannon C, Schmidt M, Labik I, Elliot H, Guo R, Asmal M, Colvin RA, Walters MC
N Engl J Med 2022 Feb 3;386(5):415-427. Epub 2021 Dec 11 doi: 10.1056/NEJMoa2113206. PMID: 34891223
Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease
N Engl J Med 2018 Jul 19;379(3):226-235. doi: 10.1056/NEJMoa1715971. PMID: 30021096
Gupta SC, Patchva S, Aggarwal BB
AAPS J 2013 Jan;15(1):195-218. Epub 2012 Nov 10 doi: 10.1208/s12248-012-9432-8. PMID: 23143785Free PMC Article

Prognosis

Calabria A, Spinozzi G, Cesana D, Buscaroli E, Benedicenti F, Pais G, Gazzo F, Scala S, Lidonnici MR, Scaramuzza S, Albertini A, Esposito S, Tucci F, Canarutto D, Omrani M, De Mattia F, Dionisio F, Giannelli S, Marktel S, Fumagalli F, Calbi V, Cenciarelli S, Ferrua F, Gentner B, Caravagna G, Ciceri F, Naldini L, Ferrari G, Aiuti A, Montini E
Nature 2024 Dec;636(8041):162-171. Epub 2024 Oct 23 doi: 10.1038/s41586-024-08250-x. PMID: 39442556Free PMC Article
Ali S, Mumtaz S, Shakir HA, Khan M, Tahir HM, Mumtaz S, Mughal TA, Hassan A, Kazmi SAR, Sadia, Irfan M, Khan MA
Mol Genet Genomic Med 2021 Dec;9(12):e1788. Epub 2021 Nov 5 doi: 10.1002/mgg3.1788. PMID: 34738740Free PMC Article
Kattamis A, Forni GL, Aydinok Y, Viprakasit V
Eur J Haematol 2020 Dec;105(6):692-703. Epub 2020 Sep 21 doi: 10.1111/ejh.13512. PMID: 32886826Free PMC Article
Wanachiwanawin W
J Pediatr Hematol Oncol 2000 Nov-Dec;22(6):581-7. doi: 10.1097/00043426-200011000-00027. PMID: 11132234
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP
N Engl J Med 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303. PMID: 7993409

Clinical prediction guides

Jaing TH, Chang TY, Chen SH, Lin CW, Wen YC, Chiu CC
Medicine (Baltimore) 2021 Nov 12;100(45):e27522. doi: 10.1097/MD.0000000000027522. PMID: 34766559Free PMC Article
Rodgers GP
Baillieres Clin Haematol 1998 Mar;11(1):239-55. doi: 10.1016/s0950-3536(98)80077-2. PMID: 10872480
Thein SL
Baillieres Clin Haematol 1998 Mar;11(1):91-126. doi: 10.1016/s0950-3536(98)80071-1. PMID: 10872474
Giardini C
Curr Opin Hematol 1997 Mar;4(2):79-87. doi: 10.1097/00062752-199704020-00002. PMID: 9107523
Camaschella C, Cappellini MD
Haematologica 1995 Jan-Feb;80(1):58-68. PMID: 7758995

Recent systematic reviews

Patsourakos D, Aggeli C, Dimitroglou Y, Delicou S, Xydaki K, Koukos M, Tsartsalis D, Gialeli F, Gatzoulis KA, Tousoulis D, Tsioufis K
Ann Hematol 2024 Sep;103(9):3335-3356. Epub 2023 Aug 1 doi: 10.1007/s00277-023-05380-6. PMID: 37526674Free PMC Article
Musallam KM, Lombard L, Kistler KD, Arregui M, Gilroy KS, Chamberlain C, Zagadailov E, Ruiz K, Taher AT
Am J Hematol 2023 Sep;98(9):1436-1451. Epub 2023 Jun 26 doi: 10.1002/ajh.27006. PMID: 37357829
Demosthenous C, Vlachaki E, Apostolou C, Eleftheriou P, Kotsiafti A, Vetsiou E, Mandala E, Perifanis V, Sarafidis P
Hematology 2019 Dec;24(1):426-438. doi: 10.1080/16078454.2019.1599096. PMID: 30947625
Algiraigri AH, Kassam A
Int J Hematol 2017 Dec;106(6):748-756. Epub 2017 Aug 7 doi: 10.1007/s12185-017-2307-0. PMID: 28786080
Liaska A, Petrou P, Georgakopoulos CD, Diamanti R, Papaconstantinou D, Kanakis MG, Georgalas I
BMC Ophthalmol 2016 Jul 8;16:102. doi: 10.1186/s12886-016-0285-2. PMID: 27390837Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG Algorithm, 2023
      ACMG Algorithm, Hemoglobin F Only or F with Decreased A: Transfusion Dependent or Non Transfusion Dependent beta-Thalassemia; Hb beta 0 Thalassemia; Hb beta+/beta+ Thalassemia; Hb beta0/beta+ Thalassemia Screening Result, 2023
    • ACMG ACT, 2023
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Hemoglobin F-Only; Hemoglobin F With Decreased A, 2023
    • ACMG ACT, 2023
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, FEA, Hemoglobin E/Beta Plus Thalassemia, 2023
    • ACMG Algorithm, 2009
      American College of Medical Genetics and Genomics, Algorithm, Hb Screening (non-S), 2009

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