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alpha Thalassemia

MedGen UID:
1434
Concept ID:
C0002312
Disease or Syndrome
Synonyms: A-Thalassemia; Alpha thalassemia spectrum
SNOMED CT: Alpha thalassemia (68913001); alpha thalassemia (68913001); Alpha thalassemia syndrome (68913001)
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).
 
Genes (locations): HBA1 (16p13.3); HBA2 (16p13.3); HBB (11p15.4)
 
Monarch Initiative: MONDO:0011399
OMIM®: 604131
Orphanet: ORPHA846

Disease characteristics

Excerpted from the GeneReview: Alpha-Thalassemia
Alpha-thalassemia (α-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome (caused by deletion/inactivation of all four alpha globin [α-globin] genes; --/--), and hemoglobin H (HbH) disease (most frequently caused by deletion/inactivation of three α-globin genes; --/-α). Hb Bart syndrome, the more severe form, is characterized by prenatal onset of generalized edema and pleural and pericardial effusions as a result of congestive heart failure induced by severe anemia. Extramedullary erythropoiesis, marked hepatosplenomegaly, and a massive placenta are common. Death usually occurs in the neonatal period. HbH disease has a broad phenotypic spectrum: although clinical features usually develop in the first years of life, HbH disease may not present until adulthood or may be diagnosed only during routine hematologic analysis in an asymptomatic individual. The majority of individuals have enlargement of the spleen (and less commonly of the liver), mild jaundice, and sometimes thalassemia-like bone changes. Individuals with HbH disease may develop gallstones and experience acute episodes of hemolysis in response to infections or exposure to oxidant drugs. [from GeneReviews]
Authors:
Hannah Tamary  |  Orly Dgany   view full author information

Additional descriptions

From OMIM
Alpha-thalassemia is one of the most common hemoglobin genetic abnormalities and is caused by the reduced or absent production of the alpha-globin chains. Four clinical conditions of increased severity are recognized: the silent carrier state (clinically and hematologically normal); thalassemia trait (microcytosis, hypochromia, and mild anemia); hemoglobin H (HbH) disease (613978; moderate to severe microcytic, hypochromic, hemolytic anemia, mild jaundice, moderate hepatosplenomegaly); and Hb Bart hydrops fetalis syndrome (severe anemia, generalized edema, ascites, marked hepatosplenomegaly, skeletal and cardiac malformations, usually death in utero) (summary by Galanello and Cao, 2011).  http://www.omim.org/entry/604131
From MedlinePlus Genetics
Alpha thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body.

In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications.

Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome, which is also called Hb Bart syndrome or alpha thalassemia major. The milder form is called HbH disease.

Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. Without treatment, most babies with this condition are stillborn or die soon after birth because of these serious health problems. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding.

HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.  https://medlineplus.gov/genetics/condition/alpha-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 alpha/beta synthesis ratio
MedGen UID:
868731
Concept ID:
C4023136
Finding
A reduction in the ratio of production of alpha globin to that of beta globin. This is the major abnormality in the various forms of alpha thalassemia.

Recent clinical studies

Etiology

Lal A, Vichinsky E
Hematol Oncol Clin North Am 2023 Apr;37(2):327-339. doi: 10.1016/j.hoc.2022.12.004. PMID: 36907606
Mensah C, Sheth S
Hematology Am Soc Hematol Educ Program 2021 Dec 10;2021(1):607-613. doi: 10.1182/hematology.2021000296. PMID: 34889395Free 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
Harteveld CL, Higgs DR
Orphanet J Rare Dis 2010 May 28;5:13. doi: 10.1186/1750-1172-5-13. PMID: 20507641Free PMC Article
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Diagnosis

Lal A, Vichinsky E
Hematol Oncol Clin North Am 2023 Apr;37(2):327-339. doi: 10.1016/j.hoc.2022.12.004. PMID: 36907606
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
Farashi S, Harteveld CL
Blood Cells Mol Dis 2018 May;70:43-53. Epub 2017 Sep 21 doi: 10.1016/j.bcmd.2017.09.004. PMID: 29032940
Piel FB, Weatherall DJ
N Engl J Med 2014 Nov 13;371(20):1908-16. doi: 10.1056/NEJMra1404415. PMID: 25390741
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Therapy

Sophâl C
Hemoglobin 2022 Jan;46(1):10-11. doi: 10.1080/03630269.2021.2008956. PMID: 35950584
Wahidiyat PA, Sari TT, Rahmartani LD, Iskandar SD, Pratanata AM, Yapiy I, Setianingsih I, Atmakusuma TD, Lubis AM
Hemoglobin 2022 Jan;46(1):39-44. doi: 10.1080/03630269.2021.2023565. PMID: 35950580
Prefumo F, Fichera A, Fratelli N, Sartori E
Best Pract Res Clin Obstet Gynaecol 2019 Jul;58:2-14. Epub 2019 Jan 9 doi: 10.1016/j.bpobgyn.2019.01.001. PMID: 30718211
Piel FB, Steinberg MH, Rees DC
N Engl J Med 2017 Apr 20;376(16):1561-1573. doi: 10.1056/NEJMra1510865. PMID: 28423290
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

Prognosis

Hsu LA, Wu S, Teng MS, Ko YL
Life Sci Alliance 2023 Dec;6(12) Epub 2023 Oct 3 doi: 10.26508/lsa.202302204. PMID: 37788909Free 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
Shafique F, Ali S, Almansouri T, Van Eeden F, Shafi N, Khalid M, Khawaja S, Andleeb S, Hassan MU
Braz J Biol 2021;83:e246062. Epub 2021 Sep 3 doi: 10.1590/1519-6984.246062. PMID: 34495151
Goonasekera HW, Paththinige CS, Dissanayake VHW
Annu Rev Genomics Hum Genet 2018 Aug 31;19:355-380. Epub 2018 May 11 doi: 10.1146/annurev-genom-091416-035451. PMID: 29751732
Brancaleoni V, Di Pierro E, Motta I, Cappellini MD
Int J Lab Hematol 2016 May;38 Suppl 1:32-40. Epub 2016 May 16 doi: 10.1111/ijlh.12527. PMID: 27183541

Clinical prediction guides

Hsu LA, Wu S, Teng MS, Ko YL
Life Sci Alliance 2023 Dec;6(12) Epub 2023 Oct 3 doi: 10.26508/lsa.202302204. PMID: 37788909Free 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
Goonasekera HW, Paththinige CS, Dissanayake VHW
Annu Rev Genomics Hum Genet 2018 Aug 31;19:355-380. Epub 2018 May 11 doi: 10.1146/annurev-genom-091416-035451. PMID: 29751732
Brancaleoni V, Di Pierro E, Motta I, Cappellini MD
Int J Lab Hematol 2016 May;38 Suppl 1:32-40. Epub 2016 May 16 doi: 10.1111/ijlh.12527. PMID: 27183541
Harteveld CL, Higgs DR
Orphanet J Rare Dis 2010 May 28;5:13. doi: 10.1186/1750-1172-5-13. PMID: 20507641Free PMC Article

Recent systematic reviews

Kirkham JK, Estepp JH, Weiss MJ, Rashkin SR
JAMA Netw Open 2023 Oct 2;6(10):e2337484. doi: 10.1001/jamanetworkopen.2023.37484. PMID: 37851445Free PMC Article
Biswas S, Gomez J, Horgan R, Sibai BM, Saad A, Powel JE, Al-Kouatly HB
Am J Obstet Gynecol MFM 2023 Sep;5(9):101067. Epub 2023 Jun 28 doi: 10.1016/j.ajogmf.2023.101067. PMID: 37385374
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
Charoenngam N, Rittiphairoj T, Ponvilawan B
Arch Osteoporos 2021 Nov 13;16(1):171. doi: 10.1007/s11657-021-01026-0. PMID: 34773506
Taylor SM, Parobek CM, Fairhurst RM
Lancet Infect Dis 2012 Jun;12(6):457-68. Epub 2012 Mar 23 doi: 10.1016/S1473-3099(12)70055-5. PMID: 22445352Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

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      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 ACT, 2023
      American College of Medical Genetics Newborn Screening ACT sheet, FA + Barts present (unquantified), FAB, Alpha Thalassemia, 2023
    • ACMG Algorithm, 2023
      ACMG Algorithm, Hemoglobin FA + Barts: Unquantified Barts Alpha Thalassemia Screening Result (FAB), 2023
    • ACMG ACT, 2023
      ACMG ACT, FA + Low/Moderate Barts Hb, FAB2, FAB1 Alpha Thalassemia: Silent carrier and alpha thalassemia trait, 2023
    • ACMG Algorithm, 2023
      ACMG Algorithm, Hemoglobin FA + Barts: Low/Moderate Barts Alpha Thalassemia Screening Result (FAB2; FAB1), 2023
    • ACMG ACT, 2012
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, FA + Barts Hb, Alpha (a) Thalassemia, 2012
    • ACMG Algorithm, 2009
      American College of Medical Genetics and Genomics, Algorithm, Hb Screening (non-S), 2009

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