U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Congenital hypoplastic anemia

MedGen UID:
266045
Concept ID:
C1260899
Disease or Syndrome
Synonyms: Aase syndrome; Anemia congenital erythroid hypoplastic; ANEMIA, CONGENITAL HYPOPLASTIC, OF BLACKFAN AND DIAMOND; Aregenerative anemia chronic congenital; Blackfan Diamond syndrome; Diamond-Blackfan anemia; Erythrogenesis imperfecta; Red cell aplasia, pure hereditary
SNOMED CT: Chronic constitutional pure red cell aplasia (88854002); Chronic constitutional pure red cell anemia (88854002); Congenital hypoplastic anemia (88854002); Congenital pure red cell anemia (88854002); Erythrogenesis imperfecta (88854002); Congenital red cell aplasia (88854002)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Related genes: TSR2, RPL35, RPS29, RPS28, RPS27, RPS26, RPS24, RPS19, RPS17, RPS15A, RPS10, RPS7, RPL35A, RPL27, RPL26, RPL18, RPL15, RPL11, RPL5
 
HPO: HP:0004810
Monarch Initiative: MONDO:0015253
OMIM® Phenotypic series: PS105650
Orphanet: ORPHA124

Disease characteristics

Excerpted from the GeneReview: Diamond-Blackfan Anemia
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. [from GeneReviews]
Authors:
Colin Sieff   view full author information

Additional description

From MedlinePlus Genetics
Diamond-Blackfan anemia is a disorder that primarily affects the bone marrow. People with this condition often also have physical abnormalities affecting various parts of the body.

The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor).

People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Individuals with Diamond-Blackfan anemia also have an increased risk of developing a bone marrow cancer known as acute myeloid leukemia (AML), a type of bone cancer called osteosarcoma, and other cancers.

Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades that are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature.

Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias).

The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with "non-classical" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms. For example, some affected individuals have mild anemia beginning later in childhood or in adulthood, while others have some of the physical features but no bone marrow problems.  https://medlineplus.gov/genetics/condition/diamond-blackfan-anemia

Term Hierarchy

Follow this link to review classifications for Congenital hypoplastic anemia in Orphanet.

Conditions with this feature

Metaphyseal chondrodysplasia, McKusick type
MedGen UID:
67398
Concept ID:
C0220748
Congenital Abnormality
The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (MDWH). Cartilage-hair hypoplasia (CHH). Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family.
Diamond-Blackfan anemia 1
MedGen UID:
390966
Concept ID:
C2676137
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.
DEGCAGS syndrome
MedGen UID:
1794177
Concept ID:
C5561967
Disease or Syndrome
DEGCAGS syndrome is an autosomal recessive syndromic neurodevelopmental disorder characterized by global developmental delay, coarse and dysmorphic facial features, and poor growth and feeding apparent from infancy. Affected individuals have variable systemic manifestations often with significant structural defects of the cardiovascular, genitourinary, gastrointestinal, and/or skeletal systems. Additional features may include sensorineural hearing loss, hypotonia, anemia or pancytopenia, and immunodeficiency with recurrent infections. Death in childhood may occur (summary by Bertoli-Avella et al., 2021).
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

Li H, Lodish HF, Sieff CA
Hematol Oncol Clin North Am 2018 Aug;32(4):701-712. Epub 2018 Jun 5 doi: 10.1016/j.hoc.2018.04.005. PMID: 30047421Free PMC Article
Raghavachar A
Blut 1990 Aug-Sep;61(2-3):47-51. doi: 10.1007/BF02076698. PMID: 1698487
Sjölin S, Wranne L
Scand J Haematol 1970;7(1):63-72. doi: 10.1111/j.1600-0609.1970.tb01870.x. PMID: 5447959

Curated

Vlachos A, Dahl N, Dianzani I, Lipton JM
Eur J Hum Genet 2011 May;19(5) Epub 2011 Jan 19 doi: 10.1038/ejhg.2010.247. PMID: 21248735Free PMC Article

Recent clinical studies

Etiology

Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Willig TN, Gazda H, Sieff CA
Curr Opin Hematol 2000 Mar;7(2):85-94. doi: 10.1097/00062752-200003000-00003. PMID: 10698294
Krijanovski OI, Sieff CA
Hematol Oncol Clin North Am 1997 Dec;11(6):1061-77. doi: 10.1016/s0889-8588(05)70483-4. PMID: 9443046
Dessypris EN
Curr Opin Hematol 1994 Mar;1(2):157-61. PMID: 9371275
Diamond LK, Wang WC, Alter BP
Adv Pediatr 1976;22:349-78. PMID: 773132

Diagnosis

Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Da Costa L, Narla A, Mohandas N
F1000Res 2018;7 Epub 2018 Aug 29 doi: 10.12688/f1000research.15542.1. PMID: 30228860Free PMC Article
Da Costa L, Willig TN, Fixler J, Mohandas N, Tchernia G
Curr Opin Pediatr 2001 Feb;13(1):10-5. doi: 10.1097/00008480-200102000-00002. PMID: 11176237
Willig TN, Gazda H, Sieff CA
Curr Opin Hematol 2000 Mar;7(2):85-94. doi: 10.1097/00062752-200003000-00003. PMID: 10698294
Krijanovski OI, Sieff CA
Hematol Oncol Clin North Am 1997 Dec;11(6):1061-77. doi: 10.1016/s0889-8588(05)70483-4. PMID: 9443046

Therapy

Gluckman E, Wagner JE
Bone Marrow Transplant 2008 Jan;41(2):127-32. Epub 2007 Dec 17 doi: 10.1038/sj.bmt.1705960. PMID: 18084332
Bizzarro MJ, Colson E, Ehrenkranz RA
Pediatr Clin North Am 2004 Aug;51(4):1087-107, xi. doi: 10.1016/j.pcl.2004.03.006. PMID: 15275990
Raghavachar A
Blut 1990 Aug-Sep;61(2-3):47-51. doi: 10.1007/BF02076698. PMID: 1698487
Diamond LK, Wang WC, Alter BP
Adv Pediatr 1976;22:349-78. PMID: 773132
Steinherz PG, Canale VC, Miller DR
Am J Med 1976 Jun;60(7):1032-5. doi: 10.1016/0002-9343(76)90576-3. PMID: 180802

Prognosis

Claassen D, Boals M, Bowling KM, Cooper GM, Cox J, Hershfield M, Lewis S, Wlodarski M, Weiss MJ, Estepp JH
Cold Spring Harb Mol Case Stud 2018 Dec;4(6) Epub 2018 Dec 17 doi: 10.1101/mcs.a003384. PMID: 30559313Free PMC Article
Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Gluckman E, Wagner JE
Bone Marrow Transplant 2008 Jan;41(2):127-32. Epub 2007 Dec 17 doi: 10.1038/sj.bmt.1705960. PMID: 18084332
Wasser JS, Yolken R, Miller DR, Diamond L
Blood 1978 May;51(5):991-5. PMID: 273451
Diamond LK, Wang WC, Alter BP
Adv Pediatr 1976;22:349-78. PMID: 773132

Clinical prediction guides

Dash CA, Madden JA, Cummings C, Rose M, Wilson SD, Mori M, Agrawal PB, Chaudhari BP, Wojcik MH
Cold Spring Harb Mol Case Stud 2023 Jun;9(3) Epub 2023 Jul 11 doi: 10.1101/mcs.a006289. PMID: 37230770Free PMC Article
Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Willig TN, Gazda H, Sieff CA
Curr Opin Hematol 2000 Mar;7(2):85-94. doi: 10.1097/00062752-200003000-00003. PMID: 10698294
Krijanovski OI, Sieff CA
Hematol Oncol Clin North Am 1997 Dec;11(6):1061-77. doi: 10.1016/s0889-8588(05)70483-4. PMID: 9443046
Dessypris EN
Curr Opin Hematol 1994 Mar;1(2):157-61. PMID: 9371275

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...