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Hemoglobin H disease(HBH)

MedGen UID:
468531
Concept ID:
C3161174
Disease or Syndrome
Synonyms: ALPHA-THALASSEMIA, HEMOGLOBIN H TYPE; HBH; HEMOGLOBIN H DISEASE, DELETIONAL
SNOMED CT: Hemoglobin H disease (48553001)
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)
 
Monarch Initiative: MONDO:0013512
OMIM®: 613978
Orphanet: ORPHA93616

Definition

Hemoglobin H disease is a subtype of alpha-thalassemia (see 604131) in which patients have compound heterozygosity for alpha(+)-thalassemia, caused by deletion of one alpha-globin gene, and for alpha(0)-thalassemia, caused by deletion in cis of 2 alpha-globin genes (summary by Lal et al., 2011). When 3 alpha-globin genes become inactive because of deletions with or without concomitant nondeletional mutations, the affected individual has only 1 functional alpha-globin gene. These people usually have moderate anemia and marked microcytosis and hypochromia. In affected adults, there is an excess of beta-globin chains within erythrocytes that will form beta-4 tetramers, also known as hemoglobin H (summary by Chui et al., 2003). Hb H disease is usually caused by the combination of alpha(0)-thalassemia with deletional alpha(+)-thalassemia, a combination referred to as 'deletional' Hb H disease. In a smaller proportion of patients, Hb H disease is caused by an alpha(0)-thalassemia plus an alpha(+)-thalassemia point mutation or small insertion/deletion. Such a situation is labeled 'nondeletional' Hb H disease. Patients with nondeletional Hb H disease are usually more anemic, more symptomatic, more prone to have significant hepatosplenomegaly, and more likely to require transfusions (summary by Lal et al., 2011). [from OMIM]

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
HbH hemoglobin
MedGen UID:
42397
Concept ID:
C0019026
Biologically Active Substance
Hemoglobin H (HbH) contains four beta-globin chains. It is normally not present at all in blood, but may make up about 1-40 percent of all hemoglobin in HbH disease, a subform of alpha thalassemia.
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.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.

Professional guidelines

PubMed

Paridar M, Azizi E, Keikhaei B, Takhviji V, Baluchi I, Khosravi A
Mol Biol Rep 2019 Oct;46(5):5041-5048. Epub 2019 Jul 4 doi: 10.1007/s11033-019-04955-9. PMID: 31273613
Lin PC, Chang TT, Liao YM, Tsai SP, Chen YC, Hsu WY, Su HL, Zeng YS, Tseng YH, Chiou SS
Lab Med 2019 Apr 8;50(2):168-173. doi: 10.1093/labmed/lmy043. PMID: 30295867
Vichinsky E
Curr Med Res Opin 2016;32(1):191-204. Epub 2015 Nov 25 doi: 10.1185/03007995.2015.1110128. PMID: 26479125

Curated

ACMG ACT, FA + High Barts Hb (>20-25% Barts) or FAB3), Alpha (a) Thalassemia: Hb H Disease

ACMG Algorithm, Hemoglobin FA + Barts: High Barts Alpha Thalassemia Screening Result (FAB3; FA + Barts > 20-25%), 2023

American College of Medical Genetics Newborn Screening ACT sheet, FA + Barts present (unquantified), FAB, Alpha Thalassemia, 2023

ACMG Algorithm, Hemoglobin FA + Barts: Unquantified Barts Alpha Thalassemia Screening Result (FAB), 2023

ACMG ACT, FA + Low/Moderate Barts Hb, FAB2, FAB1 Alpha Thalassemia: Silent carrier and alpha thalassemia trait, 2023

ACMG Algorithm, Hemoglobin FA + Barts: Low/Moderate Barts Alpha Thalassemia Screening Result (FAB2; FAB1), 2023

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, FA + Barts Hb, Alpha (a) Thalassemia, 2012

American College of Medical Genetics and Genomics, Algorithm, Hb Screening (non-S), 2009

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
Shash H
Medicina (Kaunas) 2022 Oct 21;58(10) doi: 10.3390/medicina58101496. PMID: 36295656Free PMC Article
Abolghasemi H, Kamfar S, Azarkeivan A, Karimi M, Keikhaei B, Abolghasemi F, Radfar MH, Eshghi P, Alavi S
Pediatr Hematol Oncol 2022 Sep;39(6):489-499. Epub 2021 Dec 24 doi: 10.1080/08880018.2021.2017529. PMID: 34951342
Lao TT
Best Pract Res Clin Obstet Gynaecol 2017 Feb;39:89-100. Epub 2016 Sep 23 doi: 10.1016/j.bpobgyn.2016.09.002. PMID: 28341055
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
Shash H
Medicina (Kaunas) 2022 Oct 21;58(10) doi: 10.3390/medicina58101496. PMID: 36295656Free PMC Article
Lao TT
Best Pract Res Clin Obstet Gynaecol 2017 Feb;39:89-100. Epub 2016 Sep 23 doi: 10.1016/j.bpobgyn.2016.09.002. PMID: 28341055
Musallam KM, Rivella S, Vichinsky E, Rachmilewitz EA
Haematologica 2013 Jun;98(6):833-44. doi: 10.3324/haematol.2012.066845. PMID: 23729725Free PMC Article
Muncie HL Jr, Campbell J
Am Fam Physician 2009 Aug 15;80(4):339-44. PMID: 19678601

Therapy

Su JY, Chen Y, Chen HF, Tong JR, Wei YN, Huang LL, Deng L
Eur Rev Med Pharmacol Sci 2023 Feb;27(3):1027-1032. doi: 10.26355/eurrev_202302_31198. PMID: 36808349
Shash H
Medicina (Kaunas) 2022 Oct 21;58(10) doi: 10.3390/medicina58101496. PMID: 36295656Free PMC Article
Spencer-Chapman M, Luqmani A, Layton DM, Bain BJ
Am J Hematol 2018 Jul;93(7):963-964. Epub 2018 May 6 doi: 10.1002/ajh.25072. PMID: 29473200
Vichinsky E
Curr Med Res Opin 2016;32(1):191-204. Epub 2015 Nov 25 doi: 10.1185/03007995.2015.1110128. PMID: 26479125
Yin XL, Zhang XH, Wu ZK, Zhao DH, Zhou YL, Yu YH, Liu TN, Fang SP, Zhou TH, Wang L, Huang J
Acta Haematol 2013;130(3):153-9. Epub 2013 May 22 doi: 10.1159/000347177. PMID: 23711936

Prognosis

Surapolchai P, Chuansumrit A, Sirachainan N, Kadegasem P, Leung KC, So CC
Ann Hematol 2017 Jun;96(6):1005-1014. Epub 2017 Mar 23 doi: 10.1007/s00277-017-2978-x. PMID: 28337528
Leecharoenkiat K, Sornjai W, Khungwanmaythawee K, Paemanee A, Chaichana C, Roytrakul S, Fucharoen S, Svasti S, Smith DR
Dis Markers 2014;2014:340214. Epub 2014 Jun 15 doi: 10.1155/2014/340214. PMID: 25024506Free PMC Article
Vichinsky EP
Cold Spring Harb Perspect Med 2013 May 1;3(5):a011742. doi: 10.1101/cshperspect.a011742. PMID: 23543077Free PMC Article
Weatherall DJ
Blood Rev 2012 Apr;26 Suppl 1:S3-6. doi: 10.1016/S0268-960X(12)70003-6. PMID: 22631040
Lal A, Goldrich ML, Haines DA, Azimi M, Singer ST, Vichinsky EP
N Engl J Med 2011 Feb 24;364(8):710-8. doi: 10.1056/NEJMoa1010174. PMID: 21345100

Clinical prediction guides

Qiu Y, Wei S, Hou W, Lai K, Zhu H, Li W, Li Q, Yang Z, Shu Q, Chen P, Mo W
Hemoglobin 2023 Nov;47(2):52-55. Epub 2023 Jun 12 doi: 10.1080/03630269.2023.2219008. PMID: 37309066
Wiromrat P, Rattanathongkom A, Laoaroon N, Suwannaying K, Komwilaisak P, Panamonta O, Wongsurawat N, Nasomyont N
J Clin Densitom 2023 Jul-Sep;26(3):101379. Epub 2023 Apr 26 doi: 10.1016/j.jocd.2023.101379. PMID: 37147222
He D, Kuang W, Yang X, Xu M
Clin Chem Lab Med 2021 May 26;59(6):1127-1132. Epub 2021 Jan 14 doi: 10.1515/cclm-2020-1563. PMID: 33554549
Paridar M, Azizi E, Keikhaei B, Takhviji V, Baluchi I, Khosravi A
Mol Biol Rep 2019 Oct;46(5):5041-5048. Epub 2019 Jul 4 doi: 10.1007/s11033-019-04955-9. PMID: 31273613
Galanello R, Melis MA, Furbetta M, Angius A, Rosatelli C, Cao A
Hemoglobin 1978;2(4):333-49. doi: 10.3109/03630267809005344. PMID: 701089

Recent systematic reviews

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
Kemper AR, Knapp AA, Metterville DR, Comeau AM, Green NS, Perrin JM
J Pediatr 2011 May;158(5):780-3. Epub 2010 Dec 16 doi: 10.1016/j.jpeds.2010.10.042. PMID: 21167500

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 ACT, 2023
      ACMG ACT, FA + High Barts Hb (>20-25% Barts) or FAB3), Alpha (a) Thalassemia: Hb H Disease
    • ACMG Algorithm, 2023
      ACMG Algorithm, Hemoglobin FA + Barts: High Barts Alpha Thalassemia Screening Result (FAB3; FA + Barts > 20-25%), 2023
    • 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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