U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Disease characteristics

Excerpted from the GeneReview: Beta-Thalassemia
Beta-thalassemia (β-thalassemia) has two clinically significant forms, β-thalassemia major and β-thalassemia intermedia, caused by absent or reduced synthesis of the hemoglobin subunit beta (beta globin chain). Individuals with β-thalassemia major present between ages six and 24 months with pallor due to severe anemia, poor weight gain, stunted growth, mild jaundice, and hepatosplenomegaly. Feeding problems, diarrhea, irritability, and recurrent bouts of fever may occur. Treatment with regular red blood cell transfusions and iron chelation therapy allows for normal growth and development and improves prognosis. Long-term complications associated with iron overload include stunted growth, dilated cardiomyopathy, liver disease, and endocrinopathies. Individuals with β-thalassemia intermedia have a more variable age of presentation due to milder anemia that does not require regular red blood cell transfusions from early childhood. Additional clinical features may include jaundice, cholelithiasis, hepatosplenomegaly, skeletal changes (long bone deformities, characteristic craniofacial features, and osteoporosis), leg ulcers, pulmonary hypertension, extramedullary masses of hyperplastic erythroid marrow, and increased risk of thrombotic complications. Individuals with β-thalassemia intermedia are at risk for iron overload secondary to increased intestinal absorption of iron as a result of dysregulation of iron metabolism caused by ineffective erythropoiesis. [from GeneReviews]
Authors:
Arielle L Langer   view full author information

Additional description

From MedlinePlus Genetics
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.

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.  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
Galanello R, Origa R
Orphanet J Rare Dis 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11. PMID: 20492708Free PMC Article
Cao A, Galanello R
Genet Med 2010 Feb;12(2):61-76. doi: 10.1097/GIM.0b013e3181cd68ed. PMID: 20098328
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Diagnosis

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
Asadov C, Alimirzoeva Z, Mammadova T, Aliyeva G, Gafarova S, Mammadov J
Int J Hematol 2018 Jul;108(1):5-21. Epub 2018 Jan 29 doi: 10.1007/s12185-018-2411-9. PMID: 29380178
Origa R
Genet Med 2017 Jun;19(6):609-619. Epub 2016 Nov 3 doi: 10.1038/gim.2016.173. PMID: 27811859
Cao A, Galanello R
Genet Med 2010 Feb;12(2):61-76. doi: 10.1097/GIM.0b013e3181cd68ed. PMID: 20098328
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Therapy

Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Tréluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poirée M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M
Nat Med 2022 Jan;28(1):81-88. Epub 2022 Jan 24 doi: 10.1038/s41591-021-01650-w. PMID: 35075288
Musallam KM, Bou-Fakhredin R, Cappellini MD, Taher AT
Am J Hematol 2021 Nov 1;96(11):1518-1531. Epub 2021 Aug 18 doi: 10.1002/ajh.26316. PMID: 34347889
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
Guerra A, Musallam KM, Taher AT, Rivella S
Hematol Oncol Clin North Am 2018 Apr;32(2):343-352. Epub 2017 Dec 15 doi: 10.1016/j.hoc.2017.11.002. PMID: 29458736Free PMC Article
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

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
Venugopal A, Chandran M, Eruppakotte N, Kizhakkillach S, Breezevilla SC, Vellingiri B
Mutat Res Rev Mutat Res 2018 Apr-Jun;776:23-31. Epub 2018 Mar 17 doi: 10.1016/j.mrrev.2018.03.003. PMID: 29807575
Canatan D
Hemoglobin 2014;38(5):305-7. Epub 2014 Jul 17 doi: 10.3109/03630269.2014.938163. PMID: 25030194
Rachmilewitz EA, Giardina PJ
Blood 2011 Sep 29;118(13):3479-88. Epub 2011 Aug 2 doi: 10.1182/blood-2010-08-300335. PMID: 21813448

Clinical prediction guides

Lu HY, Orkin SH, Sankaran VG
Hematol Oncol Clin North Am 2023 Apr;37(2):301-312. doi: 10.1016/j.hoc.2022.12.002. PMID: 36907604
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
Badr E, El-Sayed IT, Alasadi M
Br J Biomed Sci 2021 Jul;78(3):117-121. Epub 2021 Mar 12 doi: 10.1080/09674845.2021.1877926. PMID: 33461426
Thein SL
Blood Cells Mol Dis 2018 May;70:54-65. Epub 2017 Jun 20 doi: 10.1016/j.bcmd.2017.06.001. PMID: 28651846Free PMC Article
Thein SL
Baillieres Clin Haematol 1998 Mar;11(1):91-126. doi: 10.1016/s0950-3536(98)80071-1. PMID: 10872474

Recent systematic reviews

Manolopoulos PP, Lavranos G, Mamais I, Angouridis A, Giannakou K, Johnson EO
Osteoporos Int 2021 Jun;32(6):1031-1040. Epub 2021 Jan 9 doi: 10.1007/s00198-021-05821-w. PMID: 33423084
Zafari M, Rad MTS, Mohseni F, Nikbakht N
Hemoglobin 2021 Jan;45(1):1-4. Epub 2020 Dec 14 doi: 10.1080/03630269.2020.1857266. PMID: 33317358
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
Algiraigri AH, Wright NAM, Paolucci EO, Kassam A
Hematol Oncol Stem Cell Ther 2017 Sep;10(3):116-125. Epub 2017 Apr 6 doi: 10.1016/j.hemonc.2017.02.002. PMID: 28408107
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

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...