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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Congenital Dyserythropoietic Anemia Type I - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Congenital Dyserythropoietic Anemia Type I">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2021/07/29">
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<meta name="citation_author" content="Hannah Tamary">
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<meta name="citation_author" content="Orly Dgany">
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<meta name="citation_pmid" content="20301759">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK5313/">
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<meta name="citation_keywords" content="CDAN1-interacting nuclease 1">
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<meta name="citation_keywords" content="Codanin-1">
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<meta name="citation_keywords" content="CDAN1">
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<meta name="citation_keywords" content="CDIN1">
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<meta name="citation_keywords" content="Congenital Dyserythropoietic Anemia Type I">
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<meta name="DC.Title" content="Congenital Dyserythropoietic Anemia Type I">
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<meta name="DC.Contributor" content="Hannah Tamary">
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<meta name="DC.Contributor" content="Orly Dgany">
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<meta name="DC.Date" content="2021/07/29">
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<meta name="description" content="Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth restriction. Some individuals present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.">
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<meta name="og:description" content="Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth restriction. Some individuals present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.">
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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK5313_"><span class="title" itemprop="name">Congenital Dyserythropoietic Anemia Type I</span></h1><p class="contribs">Tamary H, Dgany O.</p><p class="fm-aai"><a href="#_NBK5313_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 17 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="cda1.Summary" itemprop="description"><h2 id="_cda1_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth restriction. Some individuals present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of CDA I is suspected based on hematologic findings and established with identification of biallelic pathogenic variants in <i>CDAN1</i> or <i>CDIN1</i>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Intramuscular or subcutaneous injections of interferon IFN-α2a or IFN-α2b are given two or three times a week or peginterferon-α2b once a week to increase hemoglobin and decrease iron overload. Allogeneic bone marrow transplantation should be considered only in transfusion-dependent persons who are resistant to IFN therapy. Treatment of iron overload using iron chelation as necessary; laparoscopic cholecystectomy for biliary stones; treatment of scoliosis per orthopedist; calcium and vitamin D supplementation for osteoporosis; treatment of extramedullary hematopoiesis including regular blood transfusions, surgical debulking, or low-dose radiation; treatment of vision issues per ophthalmologist.</p><p><i>Surveillance:</i> Measurement of hemoglobin every three to six months and more frequently at the time of infections, measurement of bilirubin, iron, transferrin, and serum ferritin concentration every six to 12 months starting at age ten years to monitor anemia and iron overload; annual myocardial and liver T<sub>2</sub>-weighted MRI starting at age ten years (if available). Annual abdominal ultrasound beginning at age five years; examination for scoliosis with orthopedist as needed; bone densitometry for osteoporosis as recommended by bone specialist; annual assessment of visual acuity and fundoscopic examination by ophthalmologist beginning at age 40 years or earlier if symptomatic.</p><p><i>Agents/circumstances to avoid:</i> Any preparation containing iron.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>CDA I is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a CDA I-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.</p></div></div><div id="cda1.Diagnosis"><h2 id="_cda1_Diagnosis_">Diagnosis</h2><div id="cda1.Suggestive_Findings"><h3>Suggestive Findings</h3><p>Congenital dyserythropoietic anemia type I (CDA I) <b>should be suspected</b> in individuals with the following laboratory and clinical findings.</p><p>
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<b>Laboratory features</b>
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</p><ul><li class="half_rhythm"><div>Moderate-to-severe macrocytic anemia with mean corpuscular volume (MCV) >90 fL in the presence of normal folic acid and serum vitamin B<sub>12</sub> levels</div></li><li class="half_rhythm"><div>Inappropriately low number of reticulocytes for the degree of anemia compared to other hemolytic anemias (secondary to ineffective erythropoiesis)</div></li><li class="half_rhythm"><div>On peripheral blood smear: macrocytosis, elliptocytes, basophilic stippling, and occasional mature nucleated erythrocytes</div></li><li class="half_rhythm"><div>In bone marrow aspirate:</div><ul><li class="half_rhythm"><div>On light microscopy, erythroid hyperplasia, few double-nucleated erythroblasts, and interchromatin bridges between erythroblasts (in 0.6%-2.8% of erythroblasts)</div></li><li class="half_rhythm"><div>On electron microscopy, erythroid precursors with spongy appearance of heterochromatin (in ≤60% of erythroblasts) and invaginations of the nuclear membrane</div></li></ul></li></ul><p>
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<b>Clinical features</b>
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</p><ul><li class="half_rhythm"><div>Jaundice</div></li><li class="half_rhythm"><div>Splenomegaly resulting from marrow expansion secondary to ineffective erythropoiesis</div></li><li class="half_rhythm"><div>Distal limb anomalies including hypoplastic nails and syndactyly</div></li></ul></div><div id="cda1.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of CDA I <b>is established</b> in a proband with <a href="#cda1.Suggestive_Findings">suggestive findings</a> and biallelic pathogenic variants in <i>CDAN1</i> or <i>CDIN1</i> identified on molecular genetic testing.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#cda1.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#cda1.Option_1">Option 1</a>), whereas those with a phenotype indistinguishable from many other inherited disorders with anemia are more likely to be diagnosed using genomic testing (see <a href="#cda1.Option_2">Option 2</a>).</p><div id="cda1.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Targeted analysis for the <a href="/books/NBK5313/table/cda1.T.congenital_dyserythropoietic_anem/?report=objectonly" target="object" rid-ob="figobcda1Tcongenitaldyserythropoieticanem">c.3124C>T</a> pathogenic variant in <i>CDAN1</i> can be performed first in individuals of Bedouin ancestry.</p><p><b>A multigene panel</b> that includes <i>CDAN1</i>, <i>CDIN1</i>, and other genes of interest (see <a href="#cda1.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</p></div><div id="cda1.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Tmoleculargenetictestingusedin"><a href="/books/NBK5313/table/cda1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobcda1Tmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.molecular_genetic_testing_used_in"><a href="/books/NBK5313/table/cda1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobcda1Tmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Congenital Dyserythropoietic Anemia Type I (CDA I) </p></div></div></div></div></div><div id="cda1.Clinical_Characteristics"><h2 id="_cda1_Clinical_Characteristics_">Clinical Characteristics</h2><div id="cda1.Clinical_Description"><h3>Clinical Description</h3><p><b>Prenatal findings.</b> Rarely, congenital dyserythropoietic anemia type I (CDA I) presents as severe in utero anemia that may be associated with hydrops fetalis, requiring intrauterine red blood cell (RBC) transfusion. Prenatal management of pregnancies at risk for complications of CDA I involves monitoring of fetal hemoglobin by Doppler ultrasonography and fetal transfusions to prevent hydrops fetalis if severe fetal anemia is detected.</p><p><b>Neonatal presentation.</b> Of 70 Bedouin neonates with CDA I, 45 (64%) were symptomatic [<a class="bibr" href="#cda1.REF.shalev.2004.746" rid="cda1.REF.shalev.2004.746">Shalev et al 2004</a>]. Of those with symptoms, 65% had hepatomegaly, 53% had early jaundice, and 27% were small for gestational age. A few had persistent pulmonary hypertension, direct hyperbilirubinemia, and transient thrombocytopenia. The majority of affected infants required at least one blood transfusion during the neonatal period.</p><p>
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<b>Childhood and later</b>
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</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Anemia.</b> Most affected individuals have lifelong moderate anemia (mean hemoglobin levels 85±6 g/L). Anemia is usually accompanied by jaundice and splenomegaly, which was present in 17 of 21 (80%) individuals [<a class="bibr" href="#cda1.REF.heimpel.2006.334" rid="cda1.REF.heimpel.2006.334">Heimpel et al 2006</a>]. Few are transfusion dependent; <a class="bibr" href="#cda1.REF.heimpel.2006.334" rid="cda1.REF.heimpel.2006.334">Heimpel et al [2006]</a> found that only two of 21 individuals followed for up to 37 years were dependent on transfusion.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Iron overload.</b> Even in those with CDA I who are not transfused, secondary hemochromatosis develops with age as a result of increased iron absorption. Free iron precipitating in parenchymal organs and especially in the heart can cause congestive heart failure and arrhythmias. Low hepcidin levels have been documented in individuals with CDA I.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Splenomegaly</b> may be absent in infants or young children but develop later with age.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Gallstones</b> were detected in four of 21 individuals before age 30 years.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Skeletal findings.</b> Distal limb anomalies including syndactyly, hypoplastic nails, and duplication of the fourth metatarsal bone were described in 4%-14% of affected individuals. Lumbar scoliosis resulting from a partly duplicated L3 vertebra was also described.</div><div class="half_rhythm">Osteoporosis was found in the majority of individuals [<a class="bibr" href="#cda1.REF.shalev.2017.13" rid="cda1.REF.shalev.2017.13">Shalev et al 2017</a>]. Progression should be monitored with bone densitometry. Treatment includes calcium and vitamin D supplementation.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Extramedullary hematopoiesis</b> (EMH) is a known complication of CDA I although the prevalence is unclear. Treatment is as in non-transfusion-dependent thalassemia, including regular blood transfusions to suppress EMH, surgical debulking, or low-dose radiation [<a class="bibr" href="#cda1.REF.taher.2017" rid="cda1.REF.taher.2017">Taher et al 2017</a>].</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Pregnancy complications.</b> A high rate of pregnancy complications was described among 28 women with CDA I, including one stillbirth, one first-trimester spontaneous abortion, and low birth weight in 42% of infants [<a class="bibr" href="#cda1.REF.shalev.2008.317" rid="cda1.REF.shalev.2008.317">Shalev et al 2008</a>]. The incidence of cæsarean section was high compared to the control group. Follow up in a high-risk pregnancy unit is therefore recommended.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Ophthalmic concerns.</b> Retinal angioid streaks with deterioration of vision have been reported as a rare complication in four adults aged 45-57 years [<a class="bibr" href="#cda1.REF.roberts.2006.456" rid="cda1.REF.roberts.2006.456">Roberts et al 2006</a>, <a class="bibr" href="#cda1.REF.tamary.2008.271" rid="cda1.REF.tamary.2008.271">Tamary et al 2008</a>, <a class="bibr" href="#cda1.REF.frimmel.2016.482" rid="cda1.REF.frimmel.2016.482">Frimmel & Kniestedt 2016</a>].</div></li></ul><p><b>Life span.</b> Five (23%) of 21 adults described by <a class="bibr" href="#cda1.REF.heimpel.2006.334" rid="cda1.REF.heimpel.2006.334">Heimpel et al [2006]</a> died, mainly as a result of iron overload. According to the authors' published follow-up data, 9% (3/32) of adults died at age 46-59 years. Causes of death included sepsis and severe arterial pulmonary hypertension [<a class="bibr" href="#cda1.REF.shalev.2017.13" rid="cda1.REF.shalev.2017.13">Shalev et al 2017</a>]. It should be noted that all deceased individuals previously underwent splenectomy.</p></div><div id="cda1.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><p>The phenotype does not differ based on associated gene.</p></div><div id="cda1.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No phenotype-genotype correlations are known. Marked clinical variability is observed even among individuals with the same pathogenic variants.</p></div><div id="cda1.Nomenclature"><h3>Nomenclature</h3><p><i>CDAN1</i>-related CDA I is also referred to as CDA type Ia. <i>CDIN1</i>-related CDA I is also referred to as CDA type Ib.</p></div><div id="cda1.Prevalence"><h3>Prevalence</h3><p>About 100 simplex cases (i.e., single occurrences in a family) – mainly from Europe – and about 70 consanguineous Israeli Bedouin families have been described in the literature. Six <i>CDIN1</i> variants have been described so far in 15 individuals [<a class="bibr" href="#cda1.REF.babbs.2013.1383" rid="cda1.REF.babbs.2013.1383">Babbs et al 2013</a>, <a class="bibr" href="#cda1.REF.palmblad.2018.e213" rid="cda1.REF.palmblad.2018.e213">Palmblad et al 2018</a>, <a class="bibr" href="#cda1.REF.rathe.2018.e26866" rid="cda1.REF.rathe.2018.e26866">Rathe et al 2018</a>, <a class="bibr" href="#cda1.REF.russo.2018.672" rid="cda1.REF.russo.2018.672">Russo et al 2018</a>, <a class="bibr" href="#cda1.REF.wang.2018.73" rid="cda1.REF.wang.2018.73">Wang et al 2018</a>, <a class="bibr" href="#cda1.REF.russo.2019.621" rid="cda1.REF.russo.2019.621">Russo et al 2019</a>.]</p></div></div><div id="cda1.Genetically_Related_Allelic_Disorde"><h2 id="_cda1_Genetically_Related_Allelic_Disorde_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>CDAN1</i> or <i>CDIN1</i>.</p></div><div id="cda1.Differential_Diagnosis"><h2 id="_cda1_Differential_Diagnosis_">Differential Diagnosis</h2><p>Congenital anemias in the differential diagnosis of congenital dyserythropoietic anemia type I (CDA I) are summarized in <a href="/books/NBK5313/table/cda1.T.congenital_anemias_of_interest_in/?report=objectonly" target="object" rid-ob="figobcda1Tcongenitalanemiasofinterestin">Table 2</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Tcongenitalanemiasofinterestin"><a href="/books/NBK5313/table/cda1.T.congenital_anemias_of_interest_in/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobcda1Tcongenitalanemiasofinterestin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.congenital_anemias_of_interest_in"><a href="/books/NBK5313/table/cda1.T.congenital_anemias_of_interest_in/?report=objectonly" target="object" rid-ob="figobcda1Tcongenitalanemiasofinterestin">Table 2. </a></h4><p class="float-caption no_bottom_margin">Congenital Anemias of Interest in the Differential Diagnosis of Congenital Dyserythropoietic Anemia Type I </p></div></div><p><b>Other.</b> The diagnosis of CDA I should be considered following exclusion of other causes of macrocytosis (mainly B<sub>12</sub> deficiency and folic acid deficiency) and dyserythropoiesis, including thalassemia syndromes and hereditary sideroblastic anemia. However, the latter two are associated with microcytic anemia.</p></div><div id="cda1.Management"><h2 id="_cda1_Management_">Management</h2><p>No clinical practice guidelines for congenital dyserythropoietic anemia type I (CDA I), have been published.</p><div id="cda1.Evaluations_Following_Initial_Diagn"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with CDA I, the evaluations summarized in <a href="/books/NBK5313/table/cda1.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobcda1Trecommendedevaluationsfollowing">Table 3</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Trecommendedevaluationsfollowing"><a href="/books/NBK5313/table/cda1.T.recommended_evaluations_following/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobcda1Trecommendedevaluationsfollowing"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.recommended_evaluations_following"><a href="/books/NBK5313/table/cda1.T.recommended_evaluations_following/?report=objectonly" target="object" rid-ob="figobcda1Trecommendedevaluationsfollowing">Table 3. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Congenital Dyserythropoietic Anemia Type I </p></div></div></div><div id="cda1.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Ttreatmentofmanifestationsinin"><a href="/books/NBK5313/table/cda1.T.treatment_of_manifestations_in_in/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobcda1Ttreatmentofmanifestationsinin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.treatment_of_manifestations_in_in"><a href="/books/NBK5313/table/cda1.T.treatment_of_manifestations_in_in/?report=objectonly" target="object" rid-ob="figobcda1Ttreatmentofmanifestationsinin">Table 4. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Congenital Dyserythropoietic Anemia Type I </p></div></div></div><div id="cda1.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Trecommendedsurveillanceforindi"><a href="/books/NBK5313/table/cda1.T.recommended_surveillance_for_indi/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobcda1Trecommendedsurveillanceforindi"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.recommended_surveillance_for_indi"><a href="/books/NBK5313/table/cda1.T.recommended_surveillance_for_indi/?report=objectonly" target="object" rid-ob="figobcda1Trecommendedsurveillanceforindi">Table 5. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Congenital Dyserythropoietic Anemia Type I </p></div></div></div><div id="cda1.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Avoid any preparation containing iron.</p></div><div id="cda1.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>Evaluation of the younger sibs of a proband for early manifestations of CDA I is recommended so that monitoring of hemoglobin and ferritin levels and treatment can begin as soon as necessary in those who are affected.</p><ul><li class="half_rhythm"><div>Evaluation of at-risk family members should include CBC to identify macrocytic anemia as well as typical findings on blood smear including macrocytosis, elliptocytes, and basophilic stippling.</div></li><li class="half_rhythm"><div>The diagnosis can be confirmed by molecular genetic testing if the pathogenic variants in the family have been identified.</div></li></ul><p>See <a href="#cda1.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="cda1.Pregnancy_Management"><h3>Pregnancy Management</h3><p>Anemia places pregnancies of affected women at high risk for delivery-related and outcome complications [<a class="bibr" href="#cda1.REF.shalev.2008.317" rid="cda1.REF.shalev.2008.317">Shalev et al 2008</a>]. Management by a high-risk obstetrics team is recommended.</p></div><div id="cda1.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.</p></div></div><div id="cda1.Genetic_Counseling"><h2 id="_cda1_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="cda1.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Congenital dyserythropoietic anemia type I (CDA I) is inherited in an autosomal recessive manner.</p></div><div id="cda1.Risk_to_Family_Members"><h3>Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes (i.e., presumed to be carriers of one CDA I-causing pathogenic variant based on family history).</div></li><li class="half_rhythm"><div>If a molecular diagnosis has been established in the proband, molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a <i>CDAN1</i> or <i>CDIN1</i> pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#cda1.REF.j_nsson.2017.519" rid="cda1.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>If both parents are known to be heterozygous for a CDA I-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Unless an individual with CDA I has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a CDA I-causing pathogenic variant.</div></li><li class="half_rhythm"><div>In populations with a high carrier rate and/or a high rate of consanguinity, it is possible that the reproductive partner of the proband is affected or is a carrier. Thus, the risk to offspring is most accurately determined after molecular genetic testing of the proband's reproductive partner (see <a href="#cda1.Prevalence">Prevalence</a>).</div></li></ul><p><b>Other family members.</b> Each sib of the proband’s parents is at a 50% risk of being a carrier of a CDA I-causing pathogenic variant.</p></div><div id="cda1.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the CDA I-causing pathogenic variants in the family.</p></div><div id="cda1.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#cda1.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative genetic alteration/s are unknown).</p></div><div id="cda1.Prenatal_Testing_and_Preimplantatio"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>If the CDA I-causing pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="cda1.Resources"><h2 id="_cda1_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>MedlinePlus</b>
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</div><div>
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<a href="https://medlineplus.gov/genetics/condition/congenital-dyserythropoietic-anemia/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Congenital dyserythropoietic anemia</a>
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</div></li></ul>
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</div><div id="cda1.Molecular_Genetics"><h2 id="_cda1_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1molgenTA"><a href="/books/NBK5313/table/cda1.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobcda1molgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.molgen.TA"><a href="/books/NBK5313/table/cda1.molgen.TA/?report=objectonly" target="object" rid-ob="figobcda1molgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Congenital Dyserythropoietic Anemia Type I: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1molgenTB"><a href="/books/NBK5313/table/cda1.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobcda1molgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.molgen.TB"><a href="/books/NBK5313/table/cda1.molgen.TB/?report=objectonly" target="object" rid-ob="figobcda1molgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Congenital Dyserythropoietic Anemia Type I (View All in OMIM) </p></div></div><div id="cda1.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>The mechanism by which pathogenic variants in <i>CDAN1</i> and <i>CDIN1</i> cause CDA type I is not completely understood. It has been shown that codanin-1 binds ASF1 histone chaperone and acts as a negative regulator of ASF1 function in chromatin assembly [<a class="bibr" href="#cda1.REF.ask.2012.2013" rid="cda1.REF.ask.2012.2013">Ask et al 2012</a>]. CDIN1 binds to codanin-1 and stabilizes its structure [<a class="bibr" href="#cda1.REF.swickley.2020.18" rid="cda1.REF.swickley.2020.18">Swickley et al 2020</a>]. It has recently also been shown that codanin-1 is essential for embryonal erythropoiesis [<a class="bibr" href="#cda1.REF.noylotan.2021.685242" rid="cda1.REF.noylotan.2021.685242">Noy-Lotan et al 2021</a>]; however, whether CDA I is directly due to abnormal chromatin assembly remains to be discovered.</p><p><b>Mechanism of disease causation.</b> Predicted loss of function</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figcda1Tcongenitaldyserythropoieticanem"><a href="/books/NBK5313/table/cda1.T.congenital_dyserythropoietic_anem/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobcda1Tcongenitaldyserythropoieticanem"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="cda1.T.congenital_dyserythropoietic_anem"><a href="/books/NBK5313/table/cda1.T.congenital_dyserythropoietic_anem/?report=objectonly" target="object" rid-ob="figobcda1Tcongenitaldyserythropoieticanem">Table 6. </a></h4><p class="float-caption no_bottom_margin">Congenital Dyserythropoietic Anemia Type I: Notable <i>CDAN1</i> Pathogenic Variants </p></div></div></div></div><div id="cda1.Chapter_Notes"><h2 id="_cda1_Chapter_Notes_">Chapter Notes</h2><div id="cda1.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>29 July 2021 (sw) Comprehensive update posted live</div></li><li class="half_rhythm"><div>25 August 2016 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>20 February 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>1 September 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>21 April 2009 (et) Review posted live</div></li><li class="half_rhythm"><div>12 November 2008 (ht) Original submission</div></li></ul></div></div><div id="cda1.References"><h2 id="_cda1_References_">References</h2><div id="cda1.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.abuquider.2020.216">Abu-Quider A, Asleh M, Shalev H, Fruchtman Y, Ben-Harosh M, Beck G, Kapelushnik J. Treatment of transfusion-dependent congenital dyserythropoietic anemia Type I patients with pegylated interferon alpha-2a. <span><span class="ref-journal">Eur J Haematol. </span>2020;<span class="ref-vol">105</span>:216–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/32302424" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32302424</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.ask.2012.2013">Ask K, Jasencakova Z, Menard P, Feng Y, Almouzni G, Groth A. Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply. <span><span class="ref-journal">EMBO J. </span>2012;<span class="ref-vol">31</span>:2013–23.</span> [<a href="/pmc/articles/PMC3343338/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3343338</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22407294" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22407294</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.ayas.2002.681">Ayas M, al-Jefri A, Baothman A, et al. Transfusion-dependent congenital dyserythropoietic anemia type I successfully treated with allogeneic stem cell transplantation. <span><span class="ref-journal">Bone Marrow Transplant. </span>2002;<span class="ref-vol">29</span>:681–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12180113" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12180113</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.babbs.2013.1383">Babbs C, Roberts NA, Sanchez-Pulido L, McGowan SJ, Ahmed MR, Brown JM, Sabry MA., WGS500 Consortium. Bentley DR, McVean GA, Donnelly P, Gileadi O, Ponting CP, Higgs DR, Buckle VJ. Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. <span><span class="ref-journal">Haematologica. </span>2013;<span class="ref-vol">98</span>:1383–7.</span> [<a href="/pmc/articles/PMC3762094/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3762094</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23716552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23716552</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.dgany.2002.1467">Dgany O, Avidan N, Delaunay J, Krasnov T, Shalmon L, Shalev H, Eidelitz-Markus T, Kapelushnik J, Cattan D, Pariente A, Tulliez M, Crétien A, Schischmanoff PO, Iolascon A, Fibach E, Koren A, Rössler J, Le Merrer M, Yaniv I, Zaizov R, Ben-Asher E, Olender T, Lancet D, Beckmann JS, Tamary H. Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. <span><span class="ref-journal">Am J Hum Genet. </span>2002;<span class="ref-vol">71</span>:1467–74.</span> [<a href="/pmc/articles/PMC378595/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC378595</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12434312" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12434312</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.frimmel.2016.482">Frimmel S, Kniestedt C. Angioid streaks in types I and II congenital dyserythropoietic anaemia (CDA). <span><span class="ref-journal">Klin Monbl Augenheilkd. </span>2016;<span class="ref-vol">233</span>:482–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27116514" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27116514</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.heimpel.2003.4576">Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K, Griesshammer A, Marquardt T, Janka-Schaub G, Kron M, Kohne E. Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation. <span><span class="ref-journal">Blood. </span>2003;<span class="ref-vol">102</span>:4576–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12933587" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12933587</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.heimpel.2006.334">Heimpel H, Schwarz K, Ebnöther M, Goede JS, Heydrich D, Kamp T, Plaumann L, Rath B, Roessler J, Schildknecht O, Schmid M, Wuillemin W, Einsiedler B, Leichtle R, Tamary H, Kohne E. Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation. <span><span class="ref-journal">Blood. </span>2006;<span class="ref-vol">107</span>:334–40.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16141353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16141353</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.iolascon.2017.1304">Iolascon A, Andolfo I, Barcellini W, Corcione F, Garçon L, De Franceschi L, Pignata C, Graziadei G, Pospisilova D, Rees DC, de Montalembert M, Rivella S, Gambale A, Russo R, Ribeiro L, Vives-Corrons J, Martinez PA, Kattamis A, Gulbis B, Cappellini MD, Roberts I, Tamary H., Working Study Group on Red Cells and Iron of the EHA. Recommendations regarding splenectomy in hereditary hemolytic anemias. <span><span class="ref-journal">Haematologica. </span>2017;<span class="ref-vol">102</span>:1304–13.</span> [<a href="/pmc/articles/PMC5541865/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5541865</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28550188" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28550188</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.j_nsson.2017.519">Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.lavabrebertrand.2004.380">Lavabre-Bertrand T, Ramos J, Delfour C, Henry L, Guiraud I, Carillo S, Wagner A, Bureau JP, Blanc P. Long-term alpha interferon treatment is effective on anaemia and significantly reduces iron overload in congenital dyserythropoiesis type I. <span><span class="ref-journal">Eur J Haematol. </span>2004;<span class="ref-vol">73</span>:380–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15458519" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15458519</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.liljeholm.2013.4791">Liljeholm M, Irvine AF, Vikberg AL, Norberg A, Month S, Sandström H, Wahlin A, Mishima M, Golovleva I. Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23. <span><span class="ref-journal">Blood. </span>2013;<span class="ref-vol">121</span>:4791–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23570799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23570799</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.m_ndez.2021.353">Méndez M, Moreno-Carralero MI, Peri VL, Camacho-Galán R, Bosch-Benítez JM, Huerta-Aragonés J, Sánchez-Calero-Guilarte J, Moreno-Risco MB, Alonso-Domínguez JM, Morán-Jiménez MJ. Congenital dyserythropoietic anemia types Ib, II, and III: novel variants in the CDIN1 gene and functional study of a novel variant in the KIF23 gene. <span><span class="ref-journal">Ann Hematol. </span>2021;<span class="ref-vol">100</span>:353–64.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/33159567" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33159567</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.miano.2019.e335">Miano M, Eikema DJ, Aljurf M, Van't Veer PJ, Öztürk G, Wölfl M, Smiers F, Schulz A, Socié G, Vettenranta K, de Heredia CD, Zecca M, Maertens J, Rovira M, Sierra J, Uckan-Cetinkaya D, Skorobogatova E, Antmen AB, Dalle JH, Markiewicz M, Hamladji RM, Kitra-Roussou V, La Nasa G, Kriván G, Al-Seiraihy A, Giardino S, Risitano AM, de Latour RP, Dufour C. Stem cell transplantation for congenital dyserythropoietic anemia: an analysis from the European Society for Blood and Marrow Transplantation. <span><span class="ref-journal">Haematologica. </span>2019;<span class="ref-vol">104</span>:e335–e339.</span> [<a href="/pmc/articles/PMC6669146/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6669146</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30679331" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30679331</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.noylotan.2021.685242">Noy-Lotan S, Dgany O, Marcoux N, Atkins A, Kupfer GM, Bosques L, Gottschalk C, Steinberg-Shemer O, Motro B, Tamary H. Cdan1 is essential for primitive erythropoiesis. <span><span class="ref-journal">Front Physiol. </span>2021;<span class="ref-vol">12</span>:685242. </span> [<a href="/pmc/articles/PMC8255688/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8255688</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/34234691" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34234691</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.palmblad.2018.e213">Palmblad J, Sander B, Bain B, Klimkowska M, Björck E. Congenital dyserythropoietic anemia type 1: a case with novel compound heterozygous mutations in the C15orf41 gene. <span><span class="ref-journal">Am J Hematol. </span>2018;<span class="ref-vol">93</span>:E213–E215.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29885034" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29885034</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.rathe.2018.e26866">Rathe M, Møller MB, Greisen PW, Fisker N. Successful management of transfusion-dependent congenital dyserythropoietic anemia type 1b with interferon alfa-2a. <span><span class="ref-journal">Pediatr Blood Cancer. </span>2018;<span class="ref-vol">65</span>:e26866. </span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29049846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29049846</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.roberts.2006.456">Roberts E, Madhusudhana KC, Newsom R, Cullis JO. Blindness due to angioid streaks in congenital dyserythropoietic anaemia type I. <span><span class="ref-journal">Br J Haematol. </span>2006;<span class="ref-vol">133</span>:456.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16681633" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16681633</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.russo.2018.672">Russo R, Andolfo I, Manna F, Gambale A, Marra R, Rosato BE, Caforio P, Pinto V, Pignataro P, Radhakrishnan K, Unal S, Tomaiuolo G, Forni GL, Iolascon A. Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. <span><span class="ref-journal">Am J Hematol. </span>2018;<span class="ref-vol">93</span>:672–82.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29396846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29396846</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.russo.2019.621">Russo R, Marra R, Andolfo I, De Rosa G, Rosato BE, Manna F, Gambale A, Raia M, Unal S, Barella S, Iolascon A. Characterization of two cases of congenital dyserythropoietic anemia type I shed light on the uncharacterized C15orf41 protein. <span><span class="ref-journal">Front Physiol. </span>2019;<span class="ref-vol">10</span>:621.</span> [<a href="/pmc/articles/PMC6539198/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6539198</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31191338" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31191338</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.shalev.2017.13">Shalev H, Al-Athamen K, Levi I, Levitas A, Tamary H. Morbidity and mortality of adult patients with congenital dyserythropoietic anemia type I. <span><span class="ref-journal">Eur J Haematol. </span>2017;<span class="ref-vol">98</span>:13–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/27206021" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27206021</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.shalev.2008.317">Shalev H, Avraham GP, Hershkovitz R, Levy A, Sheiner E, Levi I, Tamary H. Pregnancy outcome in congenital dyserythropoietic anemia type I. <span><span class="ref-journal">Eur J Haematol. </span>2008;<span class="ref-vol">81</span>:317–21.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18573172" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18573172</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.shalev.2004.746">Shalev H, Kapelushnik J, Moser A, Dgany O, Krasnov T, Tamary H. A comprehensive study of the neonatal manifestations of congenital dyserythropoietic anemia type I. <span><span class="ref-journal">J Pediatr Hematol Oncol. </span>2004;<span class="ref-vol">26</span>:746–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15543010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15543010</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.swickley.2020.18">Swickley G, Bloch Y, Malka L, Meiri A, Noy-Lotan S, Yanai A, Tamary H, Motro B. Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in congenital dyserythropoietic anemia type I disease. <span><span class="ref-journal">BMC Mol Cell Biol. </span>2020;<span class="ref-vol">21</span>:18.</span> [<a href="/pmc/articles/PMC7092493/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7092493</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32293259" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32293259</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.taher.2017">Taher A, Musallam K, Cappellini MD. Iron overload and chelation therapy. In: Weatherall D, ed. <em>Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT)</em> Chap 5. 2<sup>nd</sup> edition. Nicosia, Cyprus: Thalassaemia International Federation; 2017:39-56. [<a href="https://pubmed.ncbi.nlm.nih.gov/24672826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24672826</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.taher.2013">Taher A, Vichinsky E, Musallam K, et al. Iron overload and chelation therapy. In: Weatherall D, ed. <em>Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT)</em> Chap 5. Nicosia, Cyprus: Thalassaemia International Federation; 2013. Available online. Accessed 7-22-21. [<a href="https://pubmed.ncbi.nlm.nih.gov/24672826" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24672826</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.tamary.2008.271">Tamary H, Offret H, Dgany O, Foliguet B, Wickramasinghe SN, Krasnov T, Rumilly F, Goujard C, Fénéant-Thibault M, Cynober T, Delaunay J. Congenital dyserythropoietic anaemia, type I, in a Caucasian patient with retinal angioid streaks (homozygous Arg1042Trp mutation in codanin-1). <span><span class="ref-journal">Eur J Haematol. </span>2008;<span class="ref-vol">80</span>:271–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18081704" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18081704</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.wang.2018.73">Wang Y, Ru Y, Liu G, Dong S, Li Y, Zhu X, Zhang F, Chang YZ, Nie G. Identification of CDAN1, C15ORF41 and SEC23B mutations in Chinese patients affected by congenital dyserythropoietic anemia. <span><span class="ref-journal">Gene. </span>2018;<span class="ref-vol">640</span>:73–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29031773" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29031773</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="cda1.REF.wickramasinghe.2005.431">Wickramasinghe SN, Wood WG. Advances in the understanding of the congenital dyserythropoietic anaemias. <span><span class="ref-journal">Br J Haematol. </span>2005;<span class="ref-vol">131</span>:431–46.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16281933" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16281933</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK5313_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Hannah Tamary</span>, MD<div class="affiliation small">Professor of Pediatrics
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Director, Hematology Diagnostic and Research Laboratory
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Schneider Children's Medical Center of Israel
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Petah Tiqva, Israel<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="li.ca.uat.xeuat@yramath" class="oemail">li.ca.uat.xeuat@yramath</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Orly Dgany</span>, PhD<div class="affiliation small">Director, Pediatric Hematology Diagnostic Laboratory
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Felsenstein Medical Research Center
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Beilinson Campus
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Petah Tiqva, Israel</div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">April 21, 2009</span>; Last Update: <span itemprop="dateModified">July 29, 2021</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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Washington) are included with each copy; (ii) a link to the original material is provided
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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Tamary H, Dgany O. Congenital Dyserythropoietic Anemia Type I. 2009 Apr 21 [Updated 2021 Jul 29]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/cdg/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/cep/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobcda1Tmoleculargenetictestingusedin"><div id="cda1.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Congenital Dyserythropoietic Anemia Type I (CDA I)</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_2" style="text-align:left;vertical-align:middle;">Proportion of CDA I Attributed to Pathogenic Variants in Gene</th><th id="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>2</sup> Detectable by Method</th></tr><tr><th headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></th><th headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3" id="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>4</sup></th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CDAN1</i>
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</td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">85% <sup>5</sup></td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>6</sup></td></tr><tr><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>CDIN1</i>
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</td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~5% <sup>7</sup></td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>6</sup></td></tr><tr><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">~10%</td><td headers="hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_1_3 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_1 hd_h_cda1.T.molecular_genetic_testing_used_in_1_1_2_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:middle;">NA</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cda1.TF.1.1"><p class="no_margin">See <a href="/books/NBK5313/?report=reader#cda1.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cda1.TF.1.2"><p class="no_margin">See <a href="#cda1.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cda1.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="cda1.TF.1.4"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="cda1.TF.1.5"><p class="no_margin">In 60% of affected individuals two pathogenic variants were identified by sequence analysis, in 28% only one pathogenic variant was identified, and in 11% no pathogenic variant was identified (Note: Testing to detect splice site variants and large deletions was not performed) [Authors and other labs, combined data, unpublished].</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="cda1.TF.1.6"><p class="no_margin">No data on detection rate of gene-targeted deletion/duplication analysis are available.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="cda1.TF.1.7"><p class="no_margin">Author, personal observation</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="cda1.TF.1.8"><p class="no_margin">The existence of at least one additional locus is suggested by the absence of pathogenic variants in <i>CDAN1</i> or <i>CDIN1</i> in seven families with CDA I [<a class="bibr" href="#cda1.REF.babbs.2013.1383" rid="cda1.REF.babbs.2013.1383">Babbs et al 2013</a>].</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcda1Tcongenitalanemiasofinterestin"><div id="cda1.T.congenital_anemias_of_interest_in" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Congenital Anemias of Interest in the Differential Diagnosis of Congenital Dyserythropoietic Anemia Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.congenital_anemias_of_interest_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.congenital_anemias_of_interest_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DiffDx Disorder</th><th id="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">MOI</th><th id="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features of DiffDx Disorder</th><th id="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment/Distinguishing Features</th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>KIF23</i> <sup>1</sup></td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CDA III</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rarest CDA. The most marked anomaly in bone marrow is the presence of giant multinucleated erythroblasts w/≤12 nuclei per cell. Addl findings incl retinal angioid streaks, macular degeneration, & monoclonal gammopathy ± multiple myeloma.</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The clinical presentation is similar to that of CDA I & CDA II; however, in the reported Swedish family, the anemia is not severe & transfusions are not required.</td></tr><tr><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>KLF1</i>
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</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CDA IV (OMIM <a href="https://omim.org/entry/613673" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">613673</a>)</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AD</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Anemia of variable severity (intrauterine anemia & transfusion dependency to mild anemia). Splenomegaly is common. Peripheral blood w/↑ nucleated RBCs & bi-nucleated RBCs. MCV is usually nl. Reticulocytes usually lower compared to degree of anemia. HbF can be very high (≤40%), RBC CD44 is low.</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CDA IV has numerous nucleated RBCs on blood smear, MCV is not ↑, HbF is very high, BM EM shows erythroblasts w/cytoplasmic inclusions.</td></tr><tr><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>SEC23B</i>
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</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CDA II (HEMPAS) (OMIM <a href="https://omim.org/entry/224100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">224100</a>) <sup>2</sup></td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AR</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Most common CDA, characterized by mild-to-severe anemia, jaundice, & (in 50%-60% of affected persons) splenomegaly. ≤15% are transfusion dependent. <sup>3</sup> After age 20 yrs most develop iron overload.</td><td headers="hd_h_cda1.T.congenital_anemias_of_interest_in_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">The diagnosis of CDA II requires evidence of congenital anemia, ineffective erythropoiesis, & typical bone marrow findings w/binuclearity in 10%-50% of erythroblasts.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">AD = autosomal dominant; AR = autosomal recessive; BM = bone marrow; CDA = congenital dyserythropoietic anemia; DiffDx = differential diagnosis; EM = electron microscopy; HbF = fetal hemoglobin; MCV = mean corpuscular volume; MOI = mode of inheritance; RBC = red blood cell</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cda1.TF.2.1"><p class="no_margin"><a class="bibr" href="#cda1.REF.liljeholm.2013.4791" rid="cda1.REF.liljeholm.2013.4791">Liljeholm et al [2013]</a>, <a class="bibr" href="#cda1.REF.m_ndez.2021.353" rid="cda1.REF.m_ndez.2021.353">Méndez et al [2021]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="cda1.TF.2.2"><p class="no_margin">CDA II is also known as HEMPAS (<i>h</i>ereditary <i>e</i>rythroblastic <i>m</i>ultinuclearity with <i>p</i>ositive <i>a</i>cidified <i>s</i>erum lysis test) because the RBCs of affected individuals are lysed by acidified sera of 40%-60% of healthy adults due to the presence of natural cold-reacting IgM antibody.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="cda1.TF.2.3"><p class="no_margin"><a class="bibr" href="#cda1.REF.heimpel.2003.4576" rid="cda1.REF.heimpel.2003.4576">Heimpel et al [2003]</a>, <a class="bibr" href="#cda1.REF.wickramasinghe.2005.431" rid="cda1.REF.wickramasinghe.2005.431">Wickramasinghe & Wood [2005]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcda1Trecommendedevaluationsfollowing"><div id="cda1.T.recommended_evaluations_following" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Congenital Dyserythropoietic Anemia Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.recommended_evaluations_following/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.recommended_evaluations_following_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anemia</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hemoglobin concentration</div></li><li class="half_rhythm"><div>Serum bilirubin concentration</div></li></ul>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At diagnosis</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Iron overload</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Serum ferritin concentration</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">In persons who are not transfusion dependent beginning at age 10 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Liver & myocardial T<sub>2</sub>-weighted MRI</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Biliary stones</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound exam</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 5 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Skeletal</b>
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<br />
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<b>anomalies</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical exam for scoliosis by orthopedic surgeon</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 5-6 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Eval of osteoporosis by bone specialist</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 15 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Ophthalmic</b>
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<br />
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<b>manifestations</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ophthalmology exam incl vision assessment</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Beginning at age 40 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Genetic</b>
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<br />
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<b>counseling</b>
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</td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_cda1.T.recommended_evaluations_following_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform patients & families re nature, MOI, & implications of CDA I in order to facilitate medical & personal decision making</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CDA = congenital dyserythropoietic anemia; MOI = mode of inheritance</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="cda1.TF.3.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcda1Ttreatmentofmanifestationsinin"><div id="cda1.T.treatment_of_manifestations_in_in" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Congenital Dyserythropoietic Anemia Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.treatment_of_manifestations_in_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.treatment_of_manifestations_in_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/<br />Concern</th><th id="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Anemia</b>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Intramuscular or subcutaneous injections of IFN- <sub>α2a</sub> or IFN- <sub>α2b</sub> given 2-3x/wk or peginterferon-<sub>α2b</sub> 1x/wk [<a class="bibr" href="#cda1.REF.abuquider.2020.216" rid="cda1.REF.abuquider.2020.216">Abu-Quider et al 2020</a>]</div></li><li class="half_rhythm"><div>Treatment should be given by a physician experienced in IFN administration.</div></li></ul>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment ↑ hemoglobin & ↓ iron overload in majority of those treated [<a class="bibr" href="#cda1.REF.lavabrebertrand.2004.380" rid="cda1.REF.lavabrebertrand.2004.380">Lavabre-Bertrand et al 2004</a>]. The mechanism behind this response is unknown. To date, a limited number of persons, incl infants, have been treated.</td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Allogeneic bone marrow transplantation in transfusion-dependent persons who are resistant to IFN therapy.</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Successful transplantation described in 11 of 13 children [<a class="bibr" href="#cda1.REF.ayas.2002.681" rid="cda1.REF.ayas.2002.681">Ayas et al 2002</a>, <a class="bibr" href="#cda1.REF.miano.2019.e335" rid="cda1.REF.miano.2019.e335">Miano et al 2019</a>]</td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Splenectomy should be cautiously considered as is recommended for non-transfusion-dependent thalassemia [<a class="bibr" href="#cda1.REF.taher.2013" rid="cda1.REF.taher.2013">Taher et al 2013</a>].</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Splenectomy is of unproven value & has not been studied systematically; it failed to ↑ hemoglobin levels & also may → thromboembolic complications.</div></li><li class="half_rhythm"><div>Expert opinion by European Haematology Assoc suggested reserving splenectomy for painful splenomegaly, symptomatic thrombocytopenia, or leukopenia [<a class="bibr" href="#cda1.REF.iolascon.2017.1304" rid="cda1.REF.iolascon.2017.1304">Iolascon et al 2017</a>].</div></li></ul>
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</td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Iron overload</b>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Iron chelators as necessary</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Iron overload therapy should follow guidelines used for non-transfusion-dependent thalassemia [<a class="bibr" href="#cda1.REF.taher.2017" rid="cda1.REF.taher.2017">Taher et al 2017</a>].</td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Biliary stones</b>
|
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laparoscopic cholecystectomy</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Scoliosis</b>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per orthopedist</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Osteoporosis</b>
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|
</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Calcium & vitamin D supplementation</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Extramedullary</b>
|
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<br />
|
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<b>hematopoiesis</b>
|
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<br />
|
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<b>(EMH)</b>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Regular blood transfusions to suppress EMH, surgical debulking, or low-dose radiation</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment as recommended in non-transfusion-dependent thalassemia [<a class="bibr" href="#cda1.REF.taher.2017" rid="cda1.REF.taher.2017">Taher et al 2017</a>]</td></tr><tr><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Vision issues</b>
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</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment per ophthalmologist</td><td headers="hd_h_cda1.T.treatment_of_manifestations_in_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">IFN = interferon</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcda1Trecommendedsurveillanceforindi"><div id="cda1.T.recommended_surveillance_for_indi" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Congenital Dyserythropoietic Anemia Type I</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.recommended_surveillance_for_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.recommended_surveillance_for_indi_lrgtbl__"><table><thead><tr><th id="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Anemia</b>
|
|
</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hemoglobin</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3-6 mos, more frequent at time of infections</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Iron overload</b>
|
|
</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bilirubin, iron, transferrin & serum ferritin concentration</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos beginning at age 10 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Liver & myocardial T<sub>2</sub>-weighted MRI</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 10 yrs (if available)</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Biliary stones</b>
|
|
</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Abdominal ultrasound</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 5 yrs</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Scoliosis</b>
|
|
</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam w/orthopedist</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As needed</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Osteoporosis</b>
|
|
</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bone densitometry</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">As recommended by bone specialist</td></tr><tr><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<b>Vision issues</b>
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</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Visual acuity, fundoscopic exam</td><td headers="hd_h_cda1.T.recommended_surveillance_for_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Annually beginning at age 40 yrs, earlier if symptomatic</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcda1molgenTA"><div id="cda1.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Congenital Dyserythropoietic Anemia Type I: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_cda1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_cda1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_cda1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_cda1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_cda1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_cda1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_cda1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/146059" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CDAN1</i>
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</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=146059" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">15q15<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/Q8IWY9" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Codanin-1</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://databases.lovd.nl/shared/genes/CDAN1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDAN1 database</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CDAN1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDAN1</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CDAN1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDAN1</a>
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</td></tr><tr><td headers="hd_b_cda1.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/84529" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>CDIN1</i>
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</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=84529" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">15q14</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/Q9Y2V0" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDAN1-interacting nuclease 1</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;"></td><td headers="hd_b_cda1.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CDIN1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDIN1</a>
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</td><td headers="hd_b_cda1.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CDIN1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CDIN1</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="cda1.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobcda1molgenTB"><div id="cda1.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Congenital Dyserythropoietic Anemia Type I (<a href="/omim/224120,607465,615626,615631" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/224120" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">224120</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE Ia; CDAN1A</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/607465" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607465</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CODANIN 1; CDAN1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/615626" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">615626</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CDAN1-INTERACTING NUCLEASE 1; CDIN1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/615631" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">615631</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE Ib; CDAN1B</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobcda1Tcongenitaldyserythropoieticanem"><div id="cda1.T.congenital_dyserythropoietic_anem" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Congenital Dyserythropoietic Anemia Type I: Notable <i>CDAN1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK5313/table/cda1.T.congenital_dyserythropoietic_anem/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__cda1.T.congenital_dyserythropoietic_anem_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th><th id="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_138477.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_138477<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_612486.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_612486<wbr style="display:inline-block"></wbr>​.2</a>
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</td><td headers="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.3124C>T</td><td headers="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg1042Trp</td><td headers="hd_h_cda1.T.congenital_dyserythropoietic_anem_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Bedouin population [<a class="bibr" href="#cda1.REF.dgany.2002.1467" rid="cda1.REF.dgany.2002.1467">Dgany et al 2002</a>]</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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