MCID: HMG025
MIFTS: 39

Hemoglobin H Disease, Nondeletional

Categories: Genetic diseases, Endocrine diseases, Blood diseases, Rare diseases

Aliases & Classifications for Hemoglobin H Disease, Nondeletional

MalaCards integrated aliases for Hemoglobin H Disease, Nondeletional:

Name: Hemoglobin H Disease, Nondeletional 54 29 13
Hemoglobin H Disease 12 56 71 29 14 69
Alpha-Thalassemia Intermedia 12 56
Hbh 12 71
Alpha Thalassemia, Hemoglobin H Type 12
Alpha-Thalassemia Hemoglobin H Type 71
Hemoglobin H Disease Non-Deletional 71
Hemoglobin H Disease, Deletional 12
Hemoglobin H Disease Deletional 71
Alpha-Thalassemia 69
Hemoglobin H 29
Hbh Disease 56

Characteristics:

Orphanet epidemiological data:

56
hemoglobin h disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (United States); Age of onset: All ages;

Classifications:



External Ids:

OMIM 54 613978
Disease Ontology 12 DOID:0110031
ICD10 33 D56.0
Orphanet 56 ORPHA93616
UMLS via Orphanet 70 C3161174 C0002312 C1260396
ICD10 via Orphanet 34 D56.0
MeSH 42 D017085

Summaries for Hemoglobin H Disease, Nondeletional

OMIM : 54
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). While most thalassemia-related hydrops fetalis is caused by the lack of all alpha-globin genes, there are reports of fetuses with Hb H disease that developed the hydrops fetalis syndrome; see 236750. (613978)

MalaCards based summary : Hemoglobin H Disease, Nondeletional, also known as hemoglobin h disease, is related to alpha-thalassemia myelodysplasia syndrome, somatic and thalassemias, alpha-, and has symptoms including splenomegaly, hemolytic anemia and hepatomegaly. An important gene associated with Hemoglobin H Disease, Nondeletional is HBA2 (Hemoglobin Subunit Alpha 2), and among its related pathways/superpathways are Factors involved in megakaryocyte development and platelet production and Binding and Uptake of Ligands by Scavenger Receptors. Related phenotype is Increased shRNA abundance (Z-score > 2).

Disease Ontology : 12 An alpha thalassemia that has material basis in contiguous gene deletion of the hemoglobin alpha-1 (HBA1) and alpha-2 (HBA2) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.

UniProtKB/Swiss-Prot : 71 Hemoglobin H disease: A form of alpha-thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence.

Related Diseases for Hemoglobin H Disease, Nondeletional

Diseases related to Hemoglobin H Disease, Nondeletional via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 61)
id Related Disease Score Top Affiliating Genes
1 alpha-thalassemia myelodysplasia syndrome, somatic 11.2
2 thalassemias, alpha- 11.1
3 spastic paraplegia 16, x-linked 10.7 HBA1 HBA2
4 neuropathy, ataxia, and retinitis pigmentosa 10.7 HBA1 HBA2
5 wolman disease 10.7 HBA1 HBA2
6 paroxysmal nonkinesigenic dyskinesia 2 10.6 HBA1 HBA2
7 neuropathy, hereditary sensory and autonomic, type ic 10.6 HBA1 HBA2
8 ovarian disease 10.6 HBA1 HBA2
9 nephrotic syndrome 14 10.6 HBA2 HBB
10 bipartite talus 10.5 HBA1 HBA2
11 timothy syndrome type 2 10.5 HBA2 HBB
12 tjp2-related familial hypercholanemia 10.5 HBA2 HBB
13 hepatitis b reinfection following liver transplantation 10.4 HBB HBG1
14 unclassified vasculitis 10.4 HBB HBG1
15 tinf2-related dyskeratosis congenita 10.4 HBA2 HBB
16 methylmalonic acidemia with homocystinuria 10.4 HBA1 HBA2 HBB
17 adult-onset distal myopathy due to vcp mutation 10.4 HBB HBD
18 gaba-transaminase deficiency 10.4 HBA1 HBA2 HBB
19 distal arthrogryposis 10.4 HBA1 HBA2 HBB
20 bartholin's gland adenoma 10.4 HBB HBD
21 hepatic infarction 10.3 HBB HBD
22 algoneurodystrophy 10.3 HBA2 HBB
23 molybdenum cofactor deficiency c 10.3 HBB HBE1
24 central epithelioid sarcoma 10.3 HBB HBD
25 autosomal genetic disease 10.2 BCS1L HBB HBE1
26 intracranial structure hemangioma 10.2 HBB HBD
27 cat-scratch disease 10.2 HBA1 HBA2
28 acute leukemia 10.2 HBA2 HBB HBG1
29 voyeurism 10.2 HBB HBD
30 thalassemia 10.1
31 vagus nerve neoplasm 10.1 HBB HBE1 HBG1
32 bile duct cystadenoma 10.1 HBB HBD HBE1
33 vernal conjunctivitis 10.0 HBA1 HBA2
34 mixed malaria 10.0 HBB HBD
35 hemoglobin constant spring 10.0
36 cyanosis, transient neonatal 9.9 HBB HBD HBG1
37 hepatitis 9.9 AK1 HBA2 HBB
38 thalassemia-beta, dominant inclusion-body 9.9 HBA1 HBA2 HBB HBG1
39 hemosiderosis 9.9
40 hemoglobin quong sze 9.8
41 glucosephosphate dehydrogenase deficiency 9.7 HBB HBD HBE1 SCN2A
42 spastic paraplegia 8 9.7 HBA2 HBB HBD HBG1
43 sideroblastic anemia 9.7
44 gigantism 9.7
45 hydrops fetalis 9.7
46 splenomegaly 9.7
47 thalassemia intermedia 9.7
48 hemochromatosis 9.7
49 refractory anemia 9.7
50 leukemia 9.7

Graphical network of the top 20 diseases related to Hemoglobin H Disease, Nondeletional:



Diseases related to Hemoglobin H Disease, Nondeletional

Symptoms & Phenotypes for Hemoglobin H Disease, Nondeletional

Clinical features from OMIM:

613978

Human phenotypes related to Hemoglobin H Disease, Nondeletional:

32
id Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 hemolytic anemia 32 HP:0001878
3 hepatomegaly 32 HP:0002240
4 hemoglobin h 32 HP:0011903
5 reduced alpha/beta synthesis ratio 32 HP:0011907

GenomeRNAi Phenotypes related to Hemoglobin H Disease, Nondeletional according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-102 10.03 AK1 HBG1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-103 10.03 AK1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.03 HBA2 HBE1 AK1 HBA1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-11 10.03 BCS1L
5 Increased shRNA abundance (Z-score > 2) GR00366-A-113 10.03 HBA1 HBA2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-114 10.03 HBG1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-121 10.03 HBG1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-123 10.03 HBG1 SCN2A
9 Increased shRNA abundance (Z-score > 2) GR00366-A-133 10.03 SCN2A
10 Increased shRNA abundance (Z-score > 2) GR00366-A-140 10.03 HBA2 HBA1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-149 10.03 HBG1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10.03 SCN2A
13 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.03 ATRX BCS1L
14 Increased shRNA abundance (Z-score > 2) GR00366-A-163 10.03 HBG1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-164 10.03 HBE1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-176 10.03 HBE1
17 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.03 HBE1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-188 10.03 SCN2A
19 Increased shRNA abundance (Z-score > 2) GR00366-A-19 10.03 ATRX
20 Increased shRNA abundance (Z-score > 2) GR00366-A-205 10.03 HBA2 HBA1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-207 10.03 HBE1
22 Increased shRNA abundance (Z-score > 2) GR00366-A-23 10.03 HBE1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-29 10.03 HBG1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-35 10.03 HBG1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-41 10.03 AK1
26 Increased shRNA abundance (Z-score > 2) GR00366-A-43 10.03 AK1
27 Increased shRNA abundance (Z-score > 2) GR00366-A-46 10.03 SCN2A
28 Increased shRNA abundance (Z-score > 2) GR00366-A-47 10.03 HBG1
29 Increased shRNA abundance (Z-score > 2) GR00366-A-54 10.03 BCS1L
30 Increased shRNA abundance (Z-score > 2) GR00366-A-63 10.03 ATRX BCS1L HBG1 SCN2A
31 Increased shRNA abundance (Z-score > 2) GR00366-A-69 10.03 HBG1
32 Increased shRNA abundance (Z-score > 2) GR00366-A-73 10.03 HBE1 AK1
33 Increased shRNA abundance (Z-score > 2) GR00366-A-74 10.03 SCN2A
34 Increased shRNA abundance (Z-score > 2) GR00366-A-78 10.03 AK1
35 Increased shRNA abundance (Z-score > 2) GR00366-A-79 10.03 HBE1
36 Increased shRNA abundance (Z-score > 2) GR00366-A-85 10.03 AK1 SCN2A
37 Increased shRNA abundance (Z-score > 2) GR00366-A-9 10.03 SCN2A
38 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.91 HBG1
39 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.91 HBE1
40 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.91 HBG1
41 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 9.91 HBA1 HBA2
42 Decreased shRNA abundance (Z-score < -2) GR00366-A-193 9.91 HBG1
43 Decreased shRNA abundance (Z-score < -2) GR00366-A-204 9.91 HBE1
44 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.91 HBG1
45 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.91 HBG1
46 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.91 HBA1 HBA2
47 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.91 HBG1
48 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.91 HBA1 HBA2 HBE1 HBG1
49 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.91 HBG1
50 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.91 HBG1

Drugs & Therapeutics for Hemoglobin H Disease, Nondeletional

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Evaluating People With Thalassemia: The Thalassemia Longitudinal Cohort (TLC) Study Completed NCT00661804

Search NIH Clinical Center for Hemoglobin H Disease, Nondeletional

Genetic Tests for Hemoglobin H Disease, Nondeletional

Genetic tests related to Hemoglobin H Disease, Nondeletional:

id Genetic test Affiliating Genes
1 Hemoglobin H Disease 29
2 Hemoglobin H Disease, Nondeletional 29
3 Hemoglobin H 29

Anatomical Context for Hemoglobin H Disease, Nondeletional

Publications for Hemoglobin H Disease, Nondeletional

Variations for Hemoglobin H Disease, Nondeletional

ClinVar genetic disease variations for Hemoglobin H Disease, Nondeletional:

6 (show all 11)
id Gene Variation Type Significance SNP ID Assembly Location
1 HBA2 NM_000517.4(HBA2): c.427T> C (p.Ter143Gln) single nucleotide variant Pathogenic rs41464951 GRCh37 Chromosome 16, 223597: 223597
2 HBA2 NM_000517.4(HBA2): c.427T> A (p.Ter143Lys) single nucleotide variant Pathogenic rs41464951 GRCh37 Chromosome 16, 223597: 223597
3 HBA2 NM_000517.4(HBA2): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs121909803 GRCh37 Chromosome 16, 222912: 222912
4 HBA2 NM_000517.4(HBA2): c.*92A> G single nucleotide variant Pathogenic rs63750067 GRCh37 Chromosome 16, 223691: 223691
5 HBA2 NM_000517.4(HBA2): c.89T> C (p.Leu30Pro) single nucleotide variant Pathogenic rs41341344 GRCh37 Chromosome 16, 223000: 223000
6 HBA2 NM_000517.4(HBA2): c.429A> T (p.Ter143Tyr) single nucleotide variant Pathogenic rs41412046 GRCh37 Chromosome 16, 223599: 223599
7 HBA2 NM_000517.4(HBA2): c.314G> A (p.Cys105Tyr) single nucleotide variant Pathogenic rs41417548 GRCh37 Chromosome 16, 223484: 223484
8 HBA2 NM_000517.4(HBA2): c.301-1G> A single nucleotide variant Pathogenic rs587776827 GRCh38 Chromosome 16, 173471: 173471
9 HBA2 NM_000517.4(HBA2): c.2delT (p.Met1Argfs) deletion Pathogenic rs63750678 GRCh37 Chromosome 16, 222913: 222913
10 HBA1 NM_000558.3(HBA1): c.179G> A (p.Gly60Asp) single nucleotide variant Pathogenic rs28928878 GRCh37 Chromosome 16, 227011: 227011
11 HBA1 NM_000558.3(HBA1): c.187_189delGTG (p.Val63del) deletion Pathogenic rs35672478 GRCh37 Chromosome 16, 227019: 227021

Expression for Hemoglobin H Disease, Nondeletional

Search GEO for disease gene expression data for Hemoglobin H Disease, Nondeletional.

Pathways for Hemoglobin H Disease, Nondeletional

GO Terms for Hemoglobin H Disease, Nondeletional

Cellular components related to Hemoglobin H Disease, Nondeletional according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 blood microparticle GO:0072562 9.55 HBA1 HBA2 HBB HBD HBE1
2 endocytic vesicle lumen GO:0071682 9.43 HBA1 HBA2 HBB
3 cytosolic small ribosomal subunit GO:0022627 9.32 HBA1 HBA2
4 haptoglobin-hemoglobin complex GO:0031838 9.13 HBA1 HBA2 HBB
5 hemoglobin complex GO:0005833 9.1 HBA1 HBA2 HBB HBD HBE1 HBG1

Biological processes related to Hemoglobin H Disease, Nondeletional according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 receptor-mediated endocytosis GO:0006898 9.67 HBA1 HBA2 HBB
2 blood coagulation GO:0007596 9.62 HBB HBD HBE1 HBG1
3 cellular oxidant detoxification GO:0098869 9.61 HBA1 HBA2 HBB
4 response to hydrogen peroxide GO:0042542 9.58 HBA1 HBA2 HBB
5 positive regulation of cell death GO:0010942 9.54 HBA1 HBA2 HBB
6 Sertoli cell development GO:0060009 9.48 ATRX SOX8
7 bicarbonate transport GO:0015701 9.43 HBA1 HBA2 HBB
8 hydrogen peroxide catabolic process GO:0042744 9.33 HBA1 HBA2 HBB
9 protein heterooligomerization GO:0051291 9.26 HBA1 HBA2 HBB HBE1
10 oxygen transport GO:0015671 9.1 HBA1 HBA2 HBB HBD HBE1 HBG1
11 transport GO:0006810 10 HBA1 HBA2 HBB HBD HBE1 HBG1

Molecular functions related to Hemoglobin H Disease, Nondeletional according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 iron ion binding GO:0005506 9.73 HBA1 HBA2 HBB HBD HBE1 HBG1
2 heme binding GO:0020037 9.63 HBA1 HBA2 HBB HBD HBE1 HBG1
3 peroxidase activity GO:0004601 9.54 HBA1 HBA2 HBB
4 haptoglobin binding GO:0031720 9.5 HBA1 HBA2 HBB
5 oxygen binding GO:0019825 9.43 HBA1 HBA2 HBB HBD HBE1 HBG1
6 oxygen transporter activity GO:0005344 9.1 HBA1 HBA2 HBB HBD HBE1 HBG1

Sources for Hemoglobin H Disease, Nondeletional

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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