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Anemia of inadequate production

MedGen UID:
95937
Concept ID:
C0392708
Pathologic Function
Synonyms: Anemia, dyserythropoietic; Defective erythropoiesis; Dyserythropoietic anemia; Ineffective erythropoiesis
SNOMED CT: Ineffective erythropoiesis (70730006)
 
HPO: HP:0010972

Definition

A kind of anemia characterized by inadequate production of erythrocytes. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAnemia of inadequate production

Conditions with this feature

Myelodysplastic syndrome associated with isolated del(5q)
MedGen UID:
196625
Concept ID:
C0740302
Disease or Syndrome
The 5q- syndrome is a myelodysplastic syndrome characterized by a defect in erythroid differentiation. Patients have severe macrocytic anemia, normal or elevated platelet counts, normal or reduced neutrophil counts, erythroid hypoplasia in the bone marrow, and hypolobated micromegakaryocytes (Ebert et al., 2008).
Congenital dyserythropoietic anemia, type II
MedGen UID:
266296
Concept ID:
C1306589
Disease or Syndrome
Congenital dyserythropoietic anemia type II (CDA II) is the most common form of CDA (see this term) characterized by anemia, jaundice and splenomegaly and often leading to liver iron overload and gallstones.
Ovalocytosis, hereditary hemolytic, with defective erythropoiesis
MedGen UID:
322255
Concept ID:
C1833689
Disease or Syndrome
Majeed syndrome
MedGen UID:
351273
Concept ID:
C1864997
Disease or Syndrome
Majeed syndrome (MJDS) is an autosomal recessive pediatric multisystem autoinflammatory disorder characterized by chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia; some patients may also develop neutrophilic dermatosis. Additional features may include fever, failure to thrive, and neutropenia. Laboratory studies show elevated inflammatory markers consistent with activation of the proinflammatory IL1 (147760) pathway (summary by Ferguson and El-Shanti, 2021). Genetic Heterogeneity of Chronic Recurrent Multifocal Osteomyelitis See also CRMO2 (612852), caused by mutation in the IL1RN gene (147679) on chromosome 2q14; and CRMO3 (259680), caused by mutation in the IL1R1 gene (147810) on chromosome 2q12.
Pancreatic insufficiency-anemia-hyperostosis syndrome
MedGen UID:
436369
Concept ID:
C2675184
Disease or Syndrome
This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis. It has been described in four children, three boys and one girl, from two consanguineous families. The disease is due to a mutation in the COX4I2 gene, encoding a mitochondrial cytochrome C oxidase sub-unit. Transmission is autosomal recessive.
Congenital dyserythropoietic anemia type 4
MedGen UID:
462276
Concept ID:
C3150926
Disease or Syndrome
Congenital dyserythropoietic anemia type IV (CDAN4) is an autosomal dominant red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin (summary by Arnaud et al., 2010). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see CDAN1 (224120).
Hyperbilirubinemia, shunt, primary
MedGen UID:
763312
Concept ID:
C3550398
Disease or Syndrome
Primary shunt hyperbilirubinemia (PSHB) is a rare form of clinical jaundice characterized by increased serum levels of unconjugated bilirubin associated with ineffective erythropoiesis and a hyperplastic bone marrow. Peripheral red blood cell survival is normal (summary by Wang et al., 2006). Although primary shunt hyperbilirubinemia is clinically similar to Gilbert syndrome (143500), affected individuals do not have impaired activity of UDP-glucuronosyltransferase (UGT1A1; 191740). The term 'shunt' refers to a 'shortcut' in bilirubin production, from the bone marrow or from very young red blood cells as opposed to being derived from the hemoglobin of mature circulating erythrocytes (Israels et al., 1959).
Thrombocytopenia, X-linked, with or without dyserythropoietic anemia
MedGen UID:
763703
Concept ID:
C3550789
Disease or Syndrome
GATA1-related cytopenia is characterized by thrombocytopenia and/or anemia ranging from mild to severe. One or more of the following may also be present: platelet dysfunction, mild ß-thalassemia, neutropenia, and congenital erythropoietic porphyria (CEP) in males. Thrombocytopenia typically presents in infancy as a bleeding disorder with easy bruising and mucosal bleeding (e.g., epistaxis). Anemia ranges from minimal (mild dyserythropoiesis) to severe (hydrops fetalis requiring in utero transfusion). At the extreme end of the clinical spectrum, severe hemorrhage and/or erythrocyte transfusion dependence are life long; at the milder end, anemia and the risk for bleeding may decrease spontaneously with age. Heterozygous females may have mild-to-moderate symptoms such as menorrhagia.
Diamond-Blackfan anemia 11
MedGen UID:
766956
Concept ID:
C3554042
Disease or Syndrome
Diamond-Blackfan anemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50%, and growth deficiency in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia or no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma.
Dyserythropoiesis, congenital, with ultrastructurally normal erythroblast heterochromatin
MedGen UID:
813565
Concept ID:
C3807235
Disease or Syndrome
The congenital dyserythropoietic anemias (CDAs) are an uncommon and heterogeneous group of conditions characterized by increased ineffective erythropoiesis and, usually, dysplastic changes in erythroblasts. Originally, 3 types of CDA were recognized and designated CDA type I (224120), type II (224100), and type III (105600). Subsequently, a number of other types were described, as reviewed by Wickramasinghe (1997). The defining features of CDA type I are autosomal recessive inheritance, macrocytes in the peripheral blood, internuclear chromatin bridges connecting some almost completely separated erythroblasts, and an abnormal ultrastructural appearance (spongy or 'swiss-cheese' appearance) of the heterochromatin in a high proportion of the erythroblasts.
Congenital dyserythropoietic anemia type type 1B
MedGen UID:
816515
Concept ID:
C3810185
Disease or Syndrome
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.
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia
MedGen UID:
1615364
Concept ID:
C4540434
Disease or Syndrome
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolism due to deficiency of methylenetetrahydrofolate dehydrogenase-1. Manifestations may include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles. Folinic acid supplementation is an effective treatment (summary by Ramakrishnan et al., 2016).
X-linked sideroblastic anemia 1
MedGen UID:
1638704
Concept ID:
C4551511
Disease or Syndrome
X-linked sideroblastic anemia is an inherited disorder that prevents developing red blood cells (erythroblasts) from making enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name.\n\nThe signs and symptoms of X-linked sideroblastic anemia result from a combination of reduced hemoglobin and an overload of iron. They range from mild to severe and most often appear in young adulthood. Common features include fatigue, dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). Over time, severe medical problems such as heart disease and liver damage (cirrhosis) can result from the buildup of excess iron in these organs.
Anemia, congenital dyserythropoietic, type 1a
MedGen UID:
1807106
Concept ID:
C5574667
Disease or Syndrome
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.
Congenital dyserythropoietic anemia, type III
MedGen UID:
1801596
Concept ID:
C5676874
Disease or Syndrome
Congenital dyserythropoietic anemia type IIIa (CDAN3A) is a rare autosomal dominant hematologic disorder characterized by nonprogressive mild to moderate hemolytic anemia, macrocytosis in the peripheral blood, intravascular hemolysis, and giant multinucleated erythroblasts in the bone marrow. The disorder results from ineffective erythropoiesis. Laboratory studies show evidence of intravascular hemolysis, including increased thymidine kinase, lactate dehydrogenase, and/or undetectable haptoglobin (summary by Lind et al., 1995; Liljeholm et al., 2013). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see 224120.

Professional guidelines

PubMed

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Lane LA, Rojas-Fernandez C
Ann Pharmacother 2002 Jul-Aug;36(7-8):1268-72. doi: 10.1345/aph.1A122. PMID: 12086562
Wolff SN
Bone Marrow Transplant 2002 Apr;29(7):545-52. doi: 10.1038/sj.bmt.1703389. PMID: 11979301

Recent clinical studies

Etiology

Veras PST, de Santana MBR, Brodskyn CI, Fraga DBM, Solcà MS, De Menezes JPB, Leite BMM, Teixeira HMP
Front Cell Infect Microbiol 2023;13:1261074. Epub 2023 Oct 4 doi: 10.3389/fcimb.2023.1261074. PMID: 37860064Free PMC Article
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Ellwanger JH, Ziliotto M, Kulmann-Leal B, Chies JAB
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Cholette JM, Faraoni D, Goobie SM, Ferraris V, Hassan N
Anesth Analg 2018 Oct;127(4):1002-1016. doi: 10.1213/ANE.0000000000002504. PMID: 28991109
Schümann K, Elsenhans B, Mäurer A
J Trace Elem Med Biol 1998 Nov;12(3):129-40. doi: 10.1016/S0946-672X(98)80001-1. PMID: 9857325

Diagnosis

Veras PST, de Santana MBR, Brodskyn CI, Fraga DBM, Solcà MS, De Menezes JPB, Leite BMM, Teixeira HMP
Front Cell Infect Microbiol 2023;13:1261074. Epub 2023 Oct 4 doi: 10.3389/fcimb.2023.1261074. PMID: 37860064Free PMC Article
Joshi R, Myers E, Kokhanov A
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Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Cholette JM, Faraoni D, Goobie SM, Ferraris V, Hassan N
Anesth Analg 2018 Oct;127(4):1002-1016. doi: 10.1213/ANE.0000000000002504. PMID: 28991109
Smith HS, Elliott JA
Pain Physician 2012 Jul;15(3 Suppl):ES145-56. PMID: 22786453

Therapy

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
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Cholette JM, Faraoni D, Goobie SM, Ferraris V, Hassan N
Anesth Analg 2018 Oct;127(4):1002-1016. doi: 10.1213/ANE.0000000000002504. PMID: 28991109
Schümann K, Elsenhans B, Mäurer A
J Trace Elem Med Biol 1998 Nov;12(3):129-40. doi: 10.1016/S0946-672X(98)80001-1. PMID: 9857325

Prognosis

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Arbel Y, Milwidsky A, Finkelstein A, Halkin A, Revivo M, Berliner S, Ellis M, Herz I, Keren G, Banai S
Isr Med Assoc J 2015 Aug;17(8):500-4. PMID: 26394493
Vaziri ND
Nephrol News Issues 2014 Feb;28(2):4-5. PMID: 24649744
Lynch S
Am J Clin Nutr 2011 Aug;94(2):673S-8S. Epub 2011 Jul 6 doi: 10.3945/ajcn.110.005959. PMID: 21733878Free PMC Article
Bosman GJ, Werre JM, Willekens FL, Novotný VM
Transfus Med 2008 Dec;18(6):335-47. doi: 10.1111/j.1365-3148.2008.00892.x. PMID: 19140816

Clinical prediction guides

Rezvani A, Masoompour SM, Azarpira N, Monjazeb R, Akbarzadeh M, Salimi M, Shahriarirad R
Sci Rep 2023 Apr 28;13(1):6990. doi: 10.1038/s41598-023-34290-w. PMID: 37117600Free PMC Article
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Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Lynch S
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Bosman GJ, Werre JM, Willekens FL, Novotný VM
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Owen WF Jr
J Am Soc Nephrol 2003 Jul;14(7 Suppl 2):S76-80. doi: 10.1097/01.asn.0000070145.00225.ec. PMID: 12819307

Recent systematic reviews

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Cardiovasc Hematol Agents Med Chem 2021;19(1):83-92. doi: 10.2174/1871525718666200910161540. PMID: 32914722
Harika R, Faber M, Samuel F, Kimiywe J, Mulugeta A, Eilander A
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Markova V, Norgaard A, Jørgensen KJ, Langhoff-Roos J
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Stanworth SJ, Brunskill SJ, Hyde CJ, McClelland DB, Murphy MF
Br J Haematol 2004 Jul;126(1):139-52. doi: 10.1111/j.1365-2141.2004.04973.x. PMID: 15198745

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