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Entry
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- #613978 - HEMOGLOBIN H DISEASE; HBH
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- OMIM
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<p>
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<span class="h4">#613978</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div><a href="https://clinicaltrials.gov/search?cond=(HEMOGLOBIN H DISEASE) OR (HBA2 OR HBA1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12449&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/3294" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=613978[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
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<div id="mimNewbornScreeningFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Alpha-Thalassemia-ACT-Sheet.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/HB-Screening-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93616" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110031" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/613978" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 48553001<br />
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<strong>ORPHA:</strong> 93616<br />
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<strong>DO:</strong> 0110031<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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613978
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</span>
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</span>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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HEMOGLOBIN H DISEASE; HBH
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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ALPHA-THALASSEMIA, HEMOGLOBIN H TYPE<br />
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HEMOGLOBIN H DISEASE, DELETIONAL
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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HEMOGLOBIN H DISEASE, NONDELETIONAL, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<span class="mim-font">
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<a href="/geneMap/16/17?start=-3&limit=10&highlight=17">
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16p13.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Hemoglobin H disease, deletional and nondeletional
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/613978"> 613978 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<p>A number sign (#) is used with this entry because hemoglobin H disease is caused by contiguous gene deletion of the hemoglobin alpha-1 (HBA1; <a href="/entry/141800">141800</a>) and alpha-2 (HBA2; <a href="/entry/141850">141850</a>) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.</p>
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<p>Hemoglobin H disease is a subtype of alpha-thalassemia (see <a href="/entry/604131">604131</a>) 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 <a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al., 2011</a>). 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 <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12393486+21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>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 <a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Hemoglobin H is observed as a 'fast' electrophoretic variant. <a href="#14" class="mim-tip-reference" title="Rigas, D. A., Koler, R. D., Osgood, E. E. <strong>New hemoglobin possessing a higher electrophoretic mobility than normal adult hemoglobin.</strong> Science 121: 372 only, 1955.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13237998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13237998</a>] [<a href="https://doi.org/10.1126/science.121.3141.372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="13237998">Rigas et al. (1955)</a>, <a href="#4" class="mim-tip-reference" title="Jones, R. T., Schroeder, W. A., Balog, J. E., Vinograd, J. R. <strong>Gross structure of hemoglobin H.</strong> J. Am. Chem. Soc. 81: 3161 only, 1959."None>Jones et al. (1959)</a>, <a href="#5" class="mim-tip-reference" title="Kattamis, C., Lehmann, H. <strong>The genetical interpretation of haemoglobin H disease.</strong> Hum. Hered. 20: 156-164, 1970.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5489873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5489873</a>] [<a href="https://doi.org/10.1159/000152304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5489873">Kattamis and Lehmann (1970)</a>, <a href="#6" class="mim-tip-reference" title="Koler, R. D., Jones, R. T., Wasi, P., Pootrakul, S. N. <strong>Genetics of haemoglobin H and alpha-thalassaemia.</strong> Ann. Hum. Genet. 34: 371-377, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5579409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5579409</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1971.tb00249.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5579409">Koler et al. (1971)</a>, and <a href="#8" class="mim-tip-reference" title="Lie-Injo, L. E., Lopez, C. G., Lopes, M. <strong>Inheritance of haemoglobin H disease: a new aspect.</strong> Acta Haemat. 46: 106-120, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4331171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4331171</a>] [<a href="https://doi.org/10.1159/000208565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4331171">Lie-Injo et al. (1971)</a> provided electrophoretic observations and genetic interpretations of hemoglobin H. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5489873+5579409+4331171+13237998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Necheles, T. F., Cates, M., Sheehan, R. G., Meyer, H. J. <strong>Hemoglobin H disease. A family study.</strong> Blood 28: 501-512, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5923604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5923604</a>]" pmid="5923604">Necheles et al. (1966)</a> provided evidence that Hb H disease results from mating of a parent with alpha-thalassemia and a parent with a silent H gene, and that double heterozygosity is necessary for Hb H disease. The findings of <a href="#11" class="mim-tip-reference" title="Na-Nakorn, S., Wasi, P., Pornpatkul, M., Pootrakul, S. N. <strong>Further evidence for a genetic basis of haemoglobin H disease from newborn offspring of patients.</strong> Nature 223: 59-60, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5792424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5792424</a>] [<a href="https://doi.org/10.1038/223059a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5792424">Na-Nakorn et al. (1969)</a> led to roughly the same conclusion. Among the newborn offspring of persons with Hb H, they found some with 1 to 2% Hb Bart and others with 5 to 6%. They suggested that these 2 types of children are heterozygous for 2 different alpha-thal genes, one of which is not detectable in the adult heterozygote. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5792424+5923604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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Hb H disease is generally thought to be a mild disorder. However, there is marked phenotypic variability ranging from asymptomatic, to needing periodic transfusions, to severe anemia with hemolysis and hepatosplenomegaly, to fatal hydrops fetalis in utero. Patients with identical alpha-globin genotypes can have different phenotypes, suggesting that there are other genetic and/or environmental factors that can affect phenotypic expression of Hb H disease (summary by <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al. (2011)</a> studied 60 patients with deletional Hb H disease identified by newborn screening. Although originally assumed to be an Asian-only phenotype, among these patients 15% had 1 or both parents with African American ancestry. Growth was normal in patients with deletional Hb H during the first decade. Height-for-age percentiles for deletional Hb H patients were below the mean but above -1 Z score for children through the age of 12 years. Most children with deletional Hb H did not require blood transfusion; only 1 was required in a child under age 20 years, a 2-year-old boy with severe pneumonia who required mechanical ventilation. In patients over 20 years of age, 2 adults required transfusion: one was a 26-year-old woman with hemoglobin level of 7.6 g/dl who required transfusion during a febrile illness, and the other was a 30-year-old female who was undergoing surgery. No patients with deletional Hb H required splenectomy, and serum ferritin levels did not increase significantly between birth and 18 years. Iron overload did not generally manifest in patients with deletional Hb H prior to the third decade. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Nondeletional Hemoglobin H Disease</em></strong></p><p>
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In contrast to beta-thalassemia, nondeletional alpha(+)-thalassemia mutations are relatively uncommon. The alpha-2 globin gene (HBA2; <a href="/entry/141850">141850</a>) accounts for 2 to 3 times more alpha-globin mRNA and alpha-globin chain production than the alpha-1 gene. Therefore, point mutations of the alpha-2-globin gene generally cause more severe anemia than the same mutations involving the alpha-1-globin gene. Patients with nondeletional Hb H disease usually are more anemic, more symptomatic, more prone to have significant hepatosplenomegaly, and more likely to require transfusions (summary by <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The form of nondeletional hemoglobin H disease termed Hb H Constant Spring arises from a deletion removing both alpha-globin genes on one chromosome 16 and the alpha(+)-thalassemia mutation hemoglobin Constant Spring (X142Q; <a href="/entry/141850#0001">141850.0001</a>) on the other chromosome 16. This hemoglobinopathy is found predominantly in persons of Southeast Asian ancestry. <a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al. (2011)</a> studied 23 patients with Hb H Constant Spring. Patients with Hb H Constant Spring exhibited growth deficits beginning in infancy. Anemia was more severe in patients with Hb H Constant Spring at all ages, and acute worsening of anemia with infections requiring urgent blood transfusions was observed in patients with Hb H Constant Spring but not in those with deletional Hb H. The probability of receiving at least 1 transfusion by the age of 20 years was 3% for patients with deletional Hb H and 80% for those with Hb H Constant Spring (p less than 0.001). Among patients with Hb H Constant Spring, transfusions occurred in 13% of infants and 50% of children under the age of 6 years; splenectomy was associated with a significant improvement in hemoglobin levels (P = 0.01) and a reduction in the number of transfusions. Patients with Hb H Constant Spring were of Chinese, Laotian, and Cambodian ethnicity. Patients with Hb H Constant Spring had a very high risk of severe anemia leading to urgent blood transfusions. Transfusions were precipitated by infections in 37 events (82%) with the majority of events (60%) diagnosed as viral illness owing to an unknown source or organism. Five of 23 patients with Hb H Constant Spring underwent splenectomy between the ages of 3.9 and 13.0 years because of the need for frequent blood transfusion. The average baseline hemoglobin level before splenectomy was 6.8 (range, 6.4 to 7.4), which increased to 9.7 (range, 7.0 to 11.3) after splenectomy (P = 0.01). Splenectomy reduced or eliminated acute hemolytic episodes requiring urgent transfusion in 4 of the 5 patients. Hepatic iron was higher in patients with Hb H Constant Spring, and these patients had an increased number of annual clinic visits and increased number of annual hospital admissions by a factor of 3.9 as compared with patients with deletional hemoglobin H. <a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al. (2011)</a> stated that Hb H Constant Spring should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Hill, A. V. S., Thein, S. L., Mavo, B., Weatherall, D. J., Clegg, J. B. <strong>Non-deletion haemoglobin H disease in Papua New Guinea.</strong> J. Med. Genet. 24: 767-771, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2892939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2892939</a>] [<a href="https://doi.org/10.1136/jmg.24.12.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2892939">Hill et al. (1987)</a> described a unique nondeletion form of Hb H disease in Papua New Guinea: all 4 alpha genes were intact. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2892939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hemoglobin H Hydrops Fetalis</em></strong></p><p>
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While most thalassemia-related hydrops fetalis is caused by the lack of all alpha-globin genes (see <a href="/entry/604131">604131</a>), there are reports of fetuses with Hb H disease that developed the hydrops fetalis syndrome. For a general phenotypic description of nonimmune hydrops fetalis, see <a href="/entry/236750">236750</a>.</p><p><a href="#1" class="mim-tip-reference" title="Chan, V., Chan, V. W.-Y., Tang, M., Lau, K., Todd, D., Chan, T. K. <strong>Molecular defects in Hb H hydrops fetalis.</strong> Brit. J. Haemat. 96: 224-228, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9029003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9029003</a>] [<a href="https://doi.org/10.1046/j.1365-2141.1997.d01-2017.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9029003">Chan et al. (1997)</a> determined the molecular basis of 2 cases described as 'hemoglobin H hydrops fetalis' because they were not caused by homozygous alpha-thalassemia-1 (deletion of all 4 alpha-hemoglobin genes). Both cases were due to coinheritance of a nondeletion defect in the alpha-2 (HBA2) gene on one chromosome, at codon 30 (delta-GAG, glu; <a href="/entry/141850#0072">141850.0072</a>) and codon 59 (G-A, gly-asp; <a href="/entry/141850#0073">141850.0073</a>) respectively, and a zeta-alpha thal-1 or alpha-thal-1 genotype on the other. These 2 nondeletion defects resulted in severe anemia of the fetuses. Hb Bart levels of 31% and 39%, respectively, within the range of classic hemoglobin H disease, were present at birth. Alpha-chain production in the form of HbF and HbA totaling 66% and 48%, respectively, unlike cases of classic Hb Bart hydrops fetalis due to homozygous alpha-thalassemia-1. The second child received an intrauterine transfusion at 29 weeks' gestation and was delivered at 34 weeks. He survived a turbulent neonatal period and was discharged at 3 months. He required monthly blood transfusions and at the age of 2 years had passed normal developmental milestones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9029003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Lorey, F., Charoenkwan, P., Witkowska, H. E., Lafferty, J., Patterson, M., Eng, B., Waye, J. S., Finklestein, J. Z., Chui, D. H. K. <strong>Hb H hydrops fetalis syndrome: a case report and review of literature.</strong> Brit. J. Haemat. 115: 72-78, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11722414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11722414</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.03080.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11722414">Lorey et al. (2001)</a> reported a case of HbH hydrops fetalis syndrome caused by a point mutation in HBA2 (S35P; <a href="/entry/141850#0074">141850.0074</a>) on one chromosome and the Filipino deletion (--(FIL)), which removes all zeta- and alpha-globin genes in cis, on the other. The proband developed pericardial effusion and fetal distress and was delivered by cesarean section at 34.5 weeks' gestation, when he was observed to have severe anemia and congenital anomalies. Karyotype was 46,XY. <a href="#9" class="mim-tip-reference" title="Lorey, F., Charoenkwan, P., Witkowska, H. E., Lafferty, J., Patterson, M., Eng, B., Waye, J. S., Finklestein, J. Z., Chui, D. H. K. <strong>Hb H hydrops fetalis syndrome: a case report and review of literature.</strong> Brit. J. Haemat. 115: 72-78, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11722414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11722414</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.03080.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11722414">Lorey et al. (2001)</a> summarized 9 published cases of hemoglobin H hydrops fetalis, including their patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11722414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Hb H disease is found in many parts of the world, including Southeast Asian, Middle Eastern, and Mediterranean populations. It is particularly prevalent in Southeast Asia and in southern China, because of the high carrier frequencies of the --(SEA) deletion and to a lesser extent the --(FIL) deletion there. Of a Thailand population of 62 million people, it was estimated that 7,000 infants with Hb H disease were born annually, and that there were 420,000 patients with Hb H disease in that country (summary by <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Pressley, L., Higgs, D. R., Clegg, J. B., Perrine, R. P., Pembrey, M. E., Weatherall, D. J. <strong>A new genetic basis for hemoglobin-H disease.</strong> New Eng. J. Med. 303: 1383-1388, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6253786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6253786</a>] [<a href="https://doi.org/10.1056/NEJM198012113032402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6253786">Pressley et al. (1980)</a> showed that the form of hemoglobin H that is extraordinarily frequent in the population of the eastern Saudi Arabian oasis is the result of a different aberration of the alpha-globin haplotype than is Hb H in other populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6253786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Zeinali, S., Fallah, M.-S., Bagherian, H. <strong>Comment on heterogeneity of hemoglobin H disease in childhood. (Letter)</strong> New Eng. J. Med. 364: 2070-2071, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21612484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21612484</a>] [<a href="https://doi.org/10.1056/NEJMc1103406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21612484">Zeinali et al. (2011)</a> remarked that while unpublished data from a study of Hb H disease in Iran were consistent with the observations of <a href="#7" class="mim-tip-reference" title="Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P. <strong>Heterogeneity of hemoglobin H disease in childhood.</strong> New Eng. J. Med. 364: 710-718, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>] [<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21345100">Lal et al. (2011)</a> regarding deletional Hb H disease, those results showed more diversity in the genotype and clinical presentation of nondeletional Hb H disease. <a href="#17" class="mim-tip-reference" title="Zeinali, S., Fallah, M.-S., Bagherian, H. <strong>Comment on heterogeneity of hemoglobin H disease in childhood. (Letter)</strong> New Eng. J. Med. 364: 2070-2071, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21612484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21612484</a>] [<a href="https://doi.org/10.1056/NEJMc1103406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21612484">Zeinali et al. (2011)</a> concluded that their data and those of others consistent with it from the Mediterranean and the Middle East will be useful for clinicians treating patients from those regions in other countries. <a href="#15" class="mim-tip-reference" title="Vichinsky, E., Lal, A,. <strong>Reply to Zeinali et al. (Letter)</strong> New Eng. J. Med. 364: 2071 only, 2011."None>Vichinsky and Lal (2011)</a> replied that in general the data of <a href="#17" class="mim-tip-reference" title="Zeinali, S., Fallah, M.-S., Bagherian, H. <strong>Comment on heterogeneity of hemoglobin H disease in childhood. (Letter)</strong> New Eng. J. Med. 364: 2070-2071, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21612484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21612484</a>] [<a href="https://doi.org/10.1056/NEJMc1103406" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21612484">Zeinali et al. (2011)</a> provided support for their observations that deletional Hb H disease is relatively benign and nondeletional Hb H is moderately severe. However, many other genetic variables affect phenotype, including involvement of the alpha-2 globin gene. Environmental factors are a major determination of severity. In their study, minor febrile illnesses triggered severe anemia in patients with hemoglobin Constant Spring, and splenectomy reduced or eliminated these hemolytic events. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21612484+21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The estimated number of worldwide annual births of patients with Hb H disease is 9,568 and with Hb Bart hydrops is 5,183 (<a href="#10" class="mim-tip-reference" title="Modell, B., Darlison, M. <strong>Global epidemiology of haemoglobin disorders and derived service indicators.</strong> Bull. World Health Organ. 86: 480-487, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18568278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18568278</a>] [<a href="https://doi.org/10.2471/blt.06.036673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18568278">Modell and Darlison, 2008</a> and <a href="#16" class="mim-tip-reference" title="Weatherall, D. J. <strong>The inherited diseases of hemoglobin are an emerging global health burden.</strong> Blood 115: 4331-4336, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20233970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20233970</a>] [<a href="https://doi.org/10.1182/blood-2010-01-251348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20233970">Weatherall, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18568278+20233970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Hemoglobin H disease results from the inactivation of 3 of the 4 alpha-globin genes on both chromosomes 16. There are more than 20 known natural deletions that remove both alpha-globin genes on the same chromosome 16 (in cis) or the complete zeta-alpha-globin gene cluster, and they are known as the alpha-0-thalassemia mutations. In addition, there are rare deletions that silence alpha-globin gene expression by removing the HS-regulatory sequences upstream of the zeta-alpha-globin gene cluster (summary by <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The southeast Asian deletion of alpha-0-thalassemia, termed --(SEA), is approximately 19.3 kb and removes both alpha-globin genes in cis but spares the embryonic zeta-globin gene. This mutation is the most common cause for Hb H disease and hydrops fetalis syndrome in that part of the world. In addition, the --(FIL), --(MED), and -(alpha20.5) deletions are relatively common in the Philippines and in the Mediterranean region, respectively (summary by <a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Chui, D. H. K., Fucharoen, S., Chan, V. <strong>Hemoglobin H disease: not necessarily a benign disorder.</strong> Blood 101: 791-800, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>] [<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12393486">Chui et al. (2003)</a> reviewed the genotypes of 319 patients with Hb H disease from California, Hong Kong, and Ontario reported during the foregoing 2 years. Of those patients, 266 (83%) had deletional Hb H disease. The most common genotype was --(SEA)/-(alpha3.7), found in 175 patients (55%), followed by --(SEA)/-(alpha4.2) in 37 patients (12%), and --(FIL)/-(alpha3.7) in 36 patients (11%). Fifty-three patients (17%) had nondeletional Hb H disease. The most prevalent genotype among this subgroup was --(SEA)/Constant Spring, found in 31 patients (10%). Among the 638 chromosomes from these 319 patients, --(SEA) was found in 263 (41%), -(alpha3.7) in 224 (35%), -(alpha4.2) in 42 (7%), --(FIL) in 38 (6%), and Constant Spring in 32 chromosomes (5%). The 14 remaining mutations were found in 39 chromosomes (6%). In the Mediterranean region, the most common deletion removing both alpha-globin genes in cis is the --(MED) deletion. Among 78 Cypriot patients with Hb H disease, 79% had the --(MED) deletion and 17% had the -(alpha20.5) deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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|
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|
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<a id="1" class="mim-anchor"></a>
|
|
<a id="Chan1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, V., Chan, V. W.-Y., Tang, M., Lau, K., Todd, D., Chan, T. K.
|
|
<strong>Molecular defects in Hb H hydrops fetalis.</strong>
|
|
Brit. J. Haemat. 96: 224-228, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9029003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9029003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9029003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.1997.d01-2017.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Chui2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chui, D. H. K., Fucharoen, S., Chan, V.
|
|
<strong>Hemoglobin H disease: not necessarily a benign disorder.</strong>
|
|
Blood 101: 791-800, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12393486/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12393486</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12393486" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2002-07-1975" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Hill1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hill, A. V. S., Thein, S. L., Mavo, B., Weatherall, D. J., Clegg, J. B.
|
|
<strong>Non-deletion haemoglobin H disease in Papua New Guinea.</strong>
|
|
J. Med. Genet. 24: 767-771, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2892939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2892939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2892939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.24.12.767" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Jones1959" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jones, R. T., Schroeder, W. A., Balog, J. E., Vinograd, J. R.
|
|
<strong>Gross structure of hemoglobin H.</strong>
|
|
J. Am. Chem. Soc. 81: 3161 only, 1959.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Kattamis1970" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kattamis, C., Lehmann, H.
|
|
<strong>The genetical interpretation of haemoglobin H disease.</strong>
|
|
Hum. Hered. 20: 156-164, 1970.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5489873/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5489873</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5489873" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000152304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Koler1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koler, R. D., Jones, R. T., Wasi, P., Pootrakul, S. N.
|
|
<strong>Genetics of haemoglobin H and alpha-thalassaemia.</strong>
|
|
Ann. Hum. Genet. 34: 371-377, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5579409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5579409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5579409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1111/j.1469-1809.1971.tb00249.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Lal2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P.
|
|
<strong>Heterogeneity of hemoglobin H disease in childhood.</strong>
|
|
New Eng. J. Med. 364: 710-718, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21345100/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21345100</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21345100" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa1010174" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Lie-Injo1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lie-Injo, L. E., Lopez, C. G., Lopes, M.
|
|
<strong>Inheritance of haemoglobin H disease: a new aspect.</strong>
|
|
Acta Haemat. 46: 106-120, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4331171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4331171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4331171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000208565" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Lorey2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lorey, F., Charoenkwan, P., Witkowska, H. E., Lafferty, J., Patterson, M., Eng, B., Waye, J. S., Finklestein, J. Z., Chui, D. H. K.
|
|
<strong>Hb H hydrops fetalis syndrome: a case report and review of literature.</strong>
|
|
Brit. J. Haemat. 115: 72-78, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11722414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11722414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11722414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2001.03080.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Modell2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Modell, B., Darlison, M.
|
|
<strong>Global epidemiology of haemoglobin disorders and derived service indicators.</strong>
|
|
Bull. World Health Organ. 86: 480-487, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18568278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18568278</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18568278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.2471/blt.06.036673" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Na-Nakorn1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Na-Nakorn, S., Wasi, P., Pornpatkul, M., Pootrakul, S. N.
|
|
<strong>Further evidence for a genetic basis of haemoglobin H disease from newborn offspring of patients.</strong>
|
|
Nature 223: 59-60, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5792424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5792424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5792424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/223059a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Necheles1966" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Necheles, T. F., Cates, M., Sheehan, R. G., Meyer, H. J.
|
|
<strong>Hemoglobin H disease. A family study.</strong>
|
|
Blood 28: 501-512, 1966.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5923604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5923604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5923604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Pressley1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pressley, L., Higgs, D. R., Clegg, J. B., Perrine, R. P., Pembrey, M. E., Weatherall, D. J.
|
|
<strong>A new genetic basis for hemoglobin-H disease.</strong>
|
|
New Eng. J. Med. 303: 1383-1388, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6253786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6253786</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6253786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198012113032402" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Rigas1955" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rigas, D. A., Koler, R. D., Osgood, E. E.
|
|
<strong>New hemoglobin possessing a higher electrophoretic mobility than normal adult hemoglobin.</strong>
|
|
Science 121: 372 only, 1955.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13237998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13237998</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13237998" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1126/science.121.3141.372" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Vichinsky2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vichinsky, E., Lal, A,.
|
|
<strong>Reply to Zeinali et al. (Letter)</strong>
|
|
New Eng. J. Med. 364: 2071 only, 2011.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
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|
|
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|
|
|
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|
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|
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<a id="Weatherall2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weatherall, D. J.
|
|
<strong>The inherited diseases of hemoglobin are an emerging global health burden.</strong>
|
|
Blood 115: 4331-4336, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20233970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20233970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20233970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1182/blood-2010-01-251348" target="_blank">Full Text</a>]
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<a id="17" class="mim-anchor"></a>
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<a id="Zeinali2011" class="mim-anchor"></a>
|
|
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|
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|
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Zeinali, S., Fallah, M.-S., Bagherian, H.
|
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<strong>Comment on heterogeneity of hemoglobin H disease in childhood. (Letter)</strong>
|
|
New Eng. J. Med. 364: 2070-2071, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21612484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21612484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21612484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMc1103406" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 2/14/2013
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 11/4/2011
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Creation Date:
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<span class="mim-text-font">
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Anne M. Stumpf : 5/16/2011
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alopez : 02/14/2023
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alopez : 02/14/2023<br>alopez : 02/14/2023<br>carol : 09/10/2022<br>alopez : 02/20/2013<br>ckniffin : 2/14/2013<br>alopez : 11/4/2011<br>terry : 8/1/2011<br>terry : 8/1/2011<br>alopez : 7/27/2011<br>alopez : 7/25/2011<br>alopez : 7/25/2011
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<strong>#</strong> 613978
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HEMOGLOBIN H DISEASE; HBH
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<em>Alternative titles; symbols</em>
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ALPHA-THALASSEMIA, HEMOGLOBIN H TYPE<br />
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HEMOGLOBIN H DISEASE, DELETIONAL
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Other entities represented in this entry:
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HEMOGLOBIN H DISEASE, NONDELETIONAL, INCLUDED
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<strong>SNOMEDCT:</strong> 48553001;
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<strong>ORPHA:</strong> 93616;
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<strong>DO:</strong> 0110031;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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16p13.3
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Hemoglobin H disease, deletional and nondeletional
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613978
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3
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HBA2
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141850
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16p13.3
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Hemoglobin H disease, nondeletional
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613978
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3
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HBA1
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141800
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because hemoglobin H disease is caused by contiguous gene deletion of the hemoglobin alpha-1 (HBA1; 141800) and alpha-2 (HBA2; 141850) genes on one chromosome 16, and a defect, deletional or nondeletional, in either HBA1 or HBA2 on the other.</p>
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<strong>Description</strong>
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<p>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). </p><p>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). </p>
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<strong>Biochemical Features</strong>
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<p>Hemoglobin H is observed as a 'fast' electrophoretic variant. Rigas et al. (1955), Jones et al. (1959), Kattamis and Lehmann (1970), Koler et al. (1971), and Lie-Injo et al. (1971) provided electrophoretic observations and genetic interpretations of hemoglobin H. </p>
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<strong>Inheritance</strong>
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<p>Necheles et al. (1966) provided evidence that Hb H disease results from mating of a parent with alpha-thalassemia and a parent with a silent H gene, and that double heterozygosity is necessary for Hb H disease. The findings of Na-Nakorn et al. (1969) led to roughly the same conclusion. Among the newborn offspring of persons with Hb H, they found some with 1 to 2% Hb Bart and others with 5 to 6%. They suggested that these 2 types of children are heterozygous for 2 different alpha-thal genes, one of which is not detectable in the adult heterozygote. </p>
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<strong>Clinical Features</strong>
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<p><strong><em>Deletional Hemoglobin H Disease</em></strong></p><p>
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Hb H disease is generally thought to be a mild disorder. However, there is marked phenotypic variability ranging from asymptomatic, to needing periodic transfusions, to severe anemia with hemolysis and hepatosplenomegaly, to fatal hydrops fetalis in utero. Patients with identical alpha-globin genotypes can have different phenotypes, suggesting that there are other genetic and/or environmental factors that can affect phenotypic expression of Hb H disease (summary by Chui et al., 2003). </p><p>Lal et al. (2011) studied 60 patients with deletional Hb H disease identified by newborn screening. Although originally assumed to be an Asian-only phenotype, among these patients 15% had 1 or both parents with African American ancestry. Growth was normal in patients with deletional Hb H during the first decade. Height-for-age percentiles for deletional Hb H patients were below the mean but above -1 Z score for children through the age of 12 years. Most children with deletional Hb H did not require blood transfusion; only 1 was required in a child under age 20 years, a 2-year-old boy with severe pneumonia who required mechanical ventilation. In patients over 20 years of age, 2 adults required transfusion: one was a 26-year-old woman with hemoglobin level of 7.6 g/dl who required transfusion during a febrile illness, and the other was a 30-year-old female who was undergoing surgery. No patients with deletional Hb H required splenectomy, and serum ferritin levels did not increase significantly between birth and 18 years. Iron overload did not generally manifest in patients with deletional Hb H prior to the third decade. </p><p><strong><em>Nondeletional Hemoglobin H Disease</em></strong></p><p>
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In contrast to beta-thalassemia, nondeletional alpha(+)-thalassemia mutations are relatively uncommon. The alpha-2 globin gene (HBA2; 141850) accounts for 2 to 3 times more alpha-globin mRNA and alpha-globin chain production than the alpha-1 gene. Therefore, point mutations of the alpha-2-globin gene generally cause more severe anemia than the same mutations involving the alpha-1-globin gene. Patients with nondeletional Hb H disease usually are more anemic, more symptomatic, more prone to have significant hepatosplenomegaly, and more likely to require transfusions (summary by Chui et al., 2003). </p><p>The form of nondeletional hemoglobin H disease termed Hb H Constant Spring arises from a deletion removing both alpha-globin genes on one chromosome 16 and the alpha(+)-thalassemia mutation hemoglobin Constant Spring (X142Q; 141850.0001) on the other chromosome 16. This hemoglobinopathy is found predominantly in persons of Southeast Asian ancestry. Lal et al. (2011) studied 23 patients with Hb H Constant Spring. Patients with Hb H Constant Spring exhibited growth deficits beginning in infancy. Anemia was more severe in patients with Hb H Constant Spring at all ages, and acute worsening of anemia with infections requiring urgent blood transfusions was observed in patients with Hb H Constant Spring but not in those with deletional Hb H. The probability of receiving at least 1 transfusion by the age of 20 years was 3% for patients with deletional Hb H and 80% for those with Hb H Constant Spring (p less than 0.001). Among patients with Hb H Constant Spring, transfusions occurred in 13% of infants and 50% of children under the age of 6 years; splenectomy was associated with a significant improvement in hemoglobin levels (P = 0.01) and a reduction in the number of transfusions. Patients with Hb H Constant Spring were of Chinese, Laotian, and Cambodian ethnicity. Patients with Hb H Constant Spring had a very high risk of severe anemia leading to urgent blood transfusions. Transfusions were precipitated by infections in 37 events (82%) with the majority of events (60%) diagnosed as viral illness owing to an unknown source or organism. Five of 23 patients with Hb H Constant Spring underwent splenectomy between the ages of 3.9 and 13.0 years because of the need for frequent blood transfusion. The average baseline hemoglobin level before splenectomy was 6.8 (range, 6.4 to 7.4), which increased to 9.7 (range, 7.0 to 11.3) after splenectomy (P = 0.01). Splenectomy reduced or eliminated acute hemolytic episodes requiring urgent transfusion in 4 of the 5 patients. Hepatic iron was higher in patients with Hb H Constant Spring, and these patients had an increased number of annual clinic visits and increased number of annual hospital admissions by a factor of 3.9 as compared with patients with deletional hemoglobin H. Lal et al. (2011) stated that Hb H Constant Spring should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illness. </p><p>Hill et al. (1987) described a unique nondeletion form of Hb H disease in Papua New Guinea: all 4 alpha genes were intact. </p><p><strong><em>Hemoglobin H Hydrops Fetalis</em></strong></p><p>
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While most thalassemia-related hydrops fetalis is caused by the lack of all alpha-globin genes (see 604131), there are reports of fetuses with Hb H disease that developed the hydrops fetalis syndrome. For a general phenotypic description of nonimmune hydrops fetalis, see 236750.</p><p>Chan et al. (1997) determined the molecular basis of 2 cases described as 'hemoglobin H hydrops fetalis' because they were not caused by homozygous alpha-thalassemia-1 (deletion of all 4 alpha-hemoglobin genes). Both cases were due to coinheritance of a nondeletion defect in the alpha-2 (HBA2) gene on one chromosome, at codon 30 (delta-GAG, glu; 141850.0072) and codon 59 (G-A, gly-asp; 141850.0073) respectively, and a zeta-alpha thal-1 or alpha-thal-1 genotype on the other. These 2 nondeletion defects resulted in severe anemia of the fetuses. Hb Bart levels of 31% and 39%, respectively, within the range of classic hemoglobin H disease, were present at birth. Alpha-chain production in the form of HbF and HbA totaling 66% and 48%, respectively, unlike cases of classic Hb Bart hydrops fetalis due to homozygous alpha-thalassemia-1. The second child received an intrauterine transfusion at 29 weeks' gestation and was delivered at 34 weeks. He survived a turbulent neonatal period and was discharged at 3 months. He required monthly blood transfusions and at the age of 2 years had passed normal developmental milestones. </p><p>Lorey et al. (2001) reported a case of HbH hydrops fetalis syndrome caused by a point mutation in HBA2 (S35P; 141850.0074) on one chromosome and the Filipino deletion (--(FIL)), which removes all zeta- and alpha-globin genes in cis, on the other. The proband developed pericardial effusion and fetal distress and was delivered by cesarean section at 34.5 weeks' gestation, when he was observed to have severe anemia and congenital anomalies. Karyotype was 46,XY. Lorey et al. (2001) summarized 9 published cases of hemoglobin H hydrops fetalis, including their patient. </p>
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<strong>Population Genetics</strong>
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<p>Hb H disease is found in many parts of the world, including Southeast Asian, Middle Eastern, and Mediterranean populations. It is particularly prevalent in Southeast Asia and in southern China, because of the high carrier frequencies of the --(SEA) deletion and to a lesser extent the --(FIL) deletion there. Of a Thailand population of 62 million people, it was estimated that 7,000 infants with Hb H disease were born annually, and that there were 420,000 patients with Hb H disease in that country (summary by Chui et al., 2003). </p><p>Pressley et al. (1980) showed that the form of hemoglobin H that is extraordinarily frequent in the population of the eastern Saudi Arabian oasis is the result of a different aberration of the alpha-globin haplotype than is Hb H in other populations. </p><p>Zeinali et al. (2011) remarked that while unpublished data from a study of Hb H disease in Iran were consistent with the observations of Lal et al. (2011) regarding deletional Hb H disease, those results showed more diversity in the genotype and clinical presentation of nondeletional Hb H disease. Zeinali et al. (2011) concluded that their data and those of others consistent with it from the Mediterranean and the Middle East will be useful for clinicians treating patients from those regions in other countries. Vichinsky and Lal (2011) replied that in general the data of Zeinali et al. (2011) provided support for their observations that deletional Hb H disease is relatively benign and nondeletional Hb H is moderately severe. However, many other genetic variables affect phenotype, including involvement of the alpha-2 globin gene. Environmental factors are a major determination of severity. In their study, minor febrile illnesses triggered severe anemia in patients with hemoglobin Constant Spring, and splenectomy reduced or eliminated these hemolytic events. </p><p>The estimated number of worldwide annual births of patients with Hb H disease is 9,568 and with Hb Bart hydrops is 5,183 (Modell and Darlison, 2008 and Weatherall, 2010). </p>
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<strong>Molecular Genetics</strong>
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<p>Hemoglobin H disease results from the inactivation of 3 of the 4 alpha-globin genes on both chromosomes 16. There are more than 20 known natural deletions that remove both alpha-globin genes on the same chromosome 16 (in cis) or the complete zeta-alpha-globin gene cluster, and they are known as the alpha-0-thalassemia mutations. In addition, there are rare deletions that silence alpha-globin gene expression by removing the HS-regulatory sequences upstream of the zeta-alpha-globin gene cluster (summary by Chui et al., 2003). </p><p>The southeast Asian deletion of alpha-0-thalassemia, termed --(SEA), is approximately 19.3 kb and removes both alpha-globin genes in cis but spares the embryonic zeta-globin gene. This mutation is the most common cause for Hb H disease and hydrops fetalis syndrome in that part of the world. In addition, the --(FIL), --(MED), and -(alpha20.5) deletions are relatively common in the Philippines and in the Mediterranean region, respectively (summary by Chui et al., 2003). </p><p>Chui et al. (2003) reviewed the genotypes of 319 patients with Hb H disease from California, Hong Kong, and Ontario reported during the foregoing 2 years. Of those patients, 266 (83%) had deletional Hb H disease. The most common genotype was --(SEA)/-(alpha3.7), found in 175 patients (55%), followed by --(SEA)/-(alpha4.2) in 37 patients (12%), and --(FIL)/-(alpha3.7) in 36 patients (11%). Fifty-three patients (17%) had nondeletional Hb H disease. The most prevalent genotype among this subgroup was --(SEA)/Constant Spring, found in 31 patients (10%). Among the 638 chromosomes from these 319 patients, --(SEA) was found in 263 (41%), -(alpha3.7) in 224 (35%), -(alpha4.2) in 42 (7%), --(FIL) in 38 (6%), and Constant Spring in 32 chromosomes (5%). The 14 remaining mutations were found in 39 chromosomes (6%). In the Mediterranean region, the most common deletion removing both alpha-globin genes in cis is the --(MED) deletion. Among 78 Cypriot patients with Hb H disease, 79% had the --(MED) deletion and 17% had the -(alpha20.5) deletion. </p>
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<strong>REFERENCES</strong>
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Chan, V., Chan, V. W.-Y., Tang, M., Lau, K., Todd, D., Chan, T. K.
|
|
<strong>Molecular defects in Hb H hydrops fetalis.</strong>
|
|
Brit. J. Haemat. 96: 224-228, 1997.
|
|
|
|
|
|
[PubMed: 9029003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.1997.d01-2017.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chui, D. H. K., Fucharoen, S., Chan, V.
|
|
<strong>Hemoglobin H disease: not necessarily a benign disorder.</strong>
|
|
Blood 101: 791-800, 2003.
|
|
|
|
|
|
[PubMed: 12393486]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2002-07-1975]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hill, A. V. S., Thein, S. L., Mavo, B., Weatherall, D. J., Clegg, J. B.
|
|
<strong>Non-deletion haemoglobin H disease in Papua New Guinea.</strong>
|
|
J. Med. Genet. 24: 767-771, 1987.
|
|
|
|
|
|
[PubMed: 2892939]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.24.12.767]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jones, R. T., Schroeder, W. A., Balog, J. E., Vinograd, J. R.
|
|
<strong>Gross structure of hemoglobin H.</strong>
|
|
J. Am. Chem. Soc. 81: 3161 only, 1959.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kattamis, C., Lehmann, H.
|
|
<strong>The genetical interpretation of haemoglobin H disease.</strong>
|
|
Hum. Hered. 20: 156-164, 1970.
|
|
|
|
|
|
[PubMed: 5489873]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000152304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koler, R. D., Jones, R. T., Wasi, P., Pootrakul, S. N.
|
|
<strong>Genetics of haemoglobin H and alpha-thalassaemia.</strong>
|
|
Ann. Hum. Genet. 34: 371-377, 1971.
|
|
|
|
|
|
[PubMed: 5579409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1469-1809.1971.tb00249.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lal, A., Goldrich, M. L., Haines, D. A., Azimi, M., Singer, S. T., Vichinsky, E. P.
|
|
<strong>Heterogeneity of hemoglobin H disease in childhood.</strong>
|
|
New Eng. J. Med. 364: 710-718, 2011.
|
|
|
|
|
|
[PubMed: 21345100]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1010174]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lie-Injo, L. E., Lopez, C. G., Lopes, M.
|
|
<strong>Inheritance of haemoglobin H disease: a new aspect.</strong>
|
|
Acta Haemat. 46: 106-120, 1971.
|
|
|
|
|
|
[PubMed: 4331171]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000208565]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lorey, F., Charoenkwan, P., Witkowska, H. E., Lafferty, J., Patterson, M., Eng, B., Waye, J. S., Finklestein, J. Z., Chui, D. H. K.
|
|
<strong>Hb H hydrops fetalis syndrome: a case report and review of literature.</strong>
|
|
Brit. J. Haemat. 115: 72-78, 2001.
|
|
|
|
|
|
[PubMed: 11722414]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.03080.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Modell, B., Darlison, M.
|
|
<strong>Global epidemiology of haemoglobin disorders and derived service indicators.</strong>
|
|
Bull. World Health Organ. 86: 480-487, 2008.
|
|
|
|
|
|
[PubMed: 18568278]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2471/blt.06.036673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Na-Nakorn, S., Wasi, P., Pornpatkul, M., Pootrakul, S. N.
|
|
<strong>Further evidence for a genetic basis of haemoglobin H disease from newborn offspring of patients.</strong>
|
|
Nature 223: 59-60, 1969.
|
|
|
|
|
|
[PubMed: 5792424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/223059a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Necheles, T. F., Cates, M., Sheehan, R. G., Meyer, H. J.
|
|
<strong>Hemoglobin H disease. A family study.</strong>
|
|
Blood 28: 501-512, 1966.
|
|
|
|
|
|
[PubMed: 5923604]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pressley, L., Higgs, D. R., Clegg, J. B., Perrine, R. P., Pembrey, M. E., Weatherall, D. J.
|
|
<strong>A new genetic basis for hemoglobin-H disease.</strong>
|
|
New Eng. J. Med. 303: 1383-1388, 1980.
|
|
|
|
|
|
[PubMed: 6253786]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198012113032402]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rigas, D. A., Koler, R. D., Osgood, E. E.
|
|
<strong>New hemoglobin possessing a higher electrophoretic mobility than normal adult hemoglobin.</strong>
|
|
Science 121: 372 only, 1955.
|
|
|
|
|
|
[PubMed: 13237998]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.121.3141.372]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vichinsky, E., Lal, A,.
|
|
<strong>Reply to Zeinali et al. (Letter)</strong>
|
|
New Eng. J. Med. 364: 2071 only, 2011.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weatherall, D. J.
|
|
<strong>The inherited diseases of hemoglobin are an emerging global health burden.</strong>
|
|
Blood 115: 4331-4336, 2010.
|
|
|
|
|
|
[PubMed: 20233970]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2010-01-251348]
|
|
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|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zeinali, S., Fallah, M.-S., Bagherian, H.
|
|
<strong>Comment on heterogeneity of hemoglobin H disease in childhood. (Letter)</strong>
|
|
New Eng. J. Med. 364: 2070-2071, 2011.
|
|
|
|
|
|
[PubMed: 21612484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMc1103406]
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alopez : 02/14/2023<br>alopez : 02/14/2023<br>alopez : 02/14/2023<br>carol : 09/10/2022<br>alopez : 02/20/2013<br>ckniffin : 2/14/2013<br>alopez : 11/4/2011<br>terry : 8/1/2011<br>terry : 8/1/2011<br>alopez : 7/27/2011<br>alopez : 7/25/2011<br>alopez : 7/25/2011
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