Display Settings:

Format

Send to:

Choose Destination

Congenital dyserythropoietic anemia, type I(CDAN1A)

MedGen UID:
82891
Concept ID:
C0271933
Disease or Syndrome
Synonyms: CDA Ia; CDAN1-Related Congenital Dyserythropoietic Anemia; CDAN1A; Dyserythropoietic anemia, congenital type 1; DYSERYTHROPOIETIC ANEMIA, CONGENITAL, TYPE Ia
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Congenital dyserythropoietic anemia type I (59548005); Congenital dyserythropoietic anemia, type I (59548005)
 
Gene: CDAN1
Cytogenetic location: 15q15.2
OMIM®: 224120
Orphanet: ORPHA98869

Disease characteristics

Excerpted from the GeneReview: Congenital Dyserythropoietic Anemia Type I
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 retardation. Some cases 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. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Hannah Tamary  |  Orly Dgany   view full author information

Additional descriptions

From OMIM
CDA type I is a rare inherited red blood cell disorder characterized by macrocytic anemia, ineffective erythropoiesis, and secondary hemochromatosis. It is occasionally associated with bone abnormalities, especially of the hands and feet (acrodysostosis), nail hypoplasia, and scoliosis (Tamary et al., 2005). Striking morphologic abnormalities of erythroblasts, reviewed by Wickramasinghe and Wood (2005), include the 'Swiss-cheese' abnormality of erythroblasts on electron microscopy. Four types of CDA, all of which show show ineffective erythropoiesis and multinuclear erythroblasts, have been characterized by clinical and hematopoietic findings. The classification of the first 3 types is based on that described by Wendt and Heimpel (1967). Type I is characterized by megaloblastic changes. The more common type II (224100) is characterized by normocytic binuclear or multinuclear red cells, which on electron microscopy contain double cytoplasmic membranes. Type III (105600), which shows autosomal dominant inheritance, has prominent erythroblastic multinuclearity forming 'gigantoblasts' with up to 12 nuclei. Type IV (613673) is the designation given to a form of CDA with characteristics different from those of types I, II, and III (Wickramasinghe et al., 1991; Arnaud et al., 2010). Genetic Heterogeneity of Congenital Dyserythropoietic Anemia CDAN1B (615631) is caused by mutation in the C15ORF41 gene (615626) on chromosome 15q14; CDAN2 (224100) is caused by mutation in the SEC23B gene (610512) on chromosome 20p11; CDAN3 (105600) maps to chromosome 15q21; and CDAN4 (613673) is caused by mutation in the KLF1 gene (600599) on chromosome 19p13.  http://www.omim.org/entry/224120
From GHR
Congenital dyserythropoietic anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This disorder is one of many types of anemia, which is a condition characterized by a shortage of red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and other complications. Researchers have identified three major types of CDA: type I, type II, and type III. The types have different genetic causes and different but overlapping patterns of signs and symptoms. CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type I are born with skeletal abnormalities, most often involving the fingers and/or toes. The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis. The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). Several other variants of CDA have been described, although they appear to be rare and not much is known about them. Once researchers discover the genetic causes of these variants, some of them may be grouped with the three major types of CDA.  http://ghr.nlm.nih.gov/condition/congenital-dyserythropoietic-anemia

Clinical features

Mild postnatal growth retardation
MedGen UID:
500907
Concept ID:
CN001397
Finding
A mild degree of slow or limited growth after birth, being between two and three standard deviations below age- and sex-related norms.
Syndactyly
MedGen UID:
776571
Concept ID:
C2117411
Finding
Hydrops fetalis
MedGen UID:
504951
Concept ID:
CN001623
Finding
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Prolonged neonatal jaundice
MedGen UID:
505938
Concept ID:
CN005732
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Prolonged neonatal jaundice
MedGen UID:
505938
Concept ID:
CN005732
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Reticulocytosis
MedGen UID:
60089
Concept ID:
C0206160
Finding
An increase in circulating RETICULOCYTES, which is among the simplest and most reliable signs of accelerated ERYTHROCYTE production. Reticulocytosis occurs during active BLOOD regeneration (stimulation of red bone marrow) and in certain types of ANEMIA, particularly CONGENITAL HEMOLYTIC ANEMIA.
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
The presence of erythrocytes with excessive variation in size in the blood.
Poikilocytosis
MedGen UID:
67451
Concept ID:
C0221281
Finding
An increase in the number of abnormally shaped red blood cells.
Erythroid hyperplasia
MedGen UID:
333017
Concept ID:
C1838111
Finding
Macrocytic dyserythropoietic anemia
MedGen UID:
428153
Concept ID:
CN004900
Finding
Hydrops fetalis
MedGen UID:
504951
Concept ID:
CN001623
Finding
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Endopolyploidy on chromosome studies of bone marrow
MedGen UID:
425141
Concept ID:
CN003026
Finding
An increase in the number of chromosome sets per cell in bone marrow cells.
Reduced activity of N-acetylglucosaminyltransferase II
MedGen UID:
425153
Concept ID:
CN003303
Finding
An abnormality of glycoprotein metabolism related to a decreased rate of alpha-1,6-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Syndactyly
MedGen UID:
776571
Concept ID:
C2117411
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGCongenital dyserythropoietic anemia, type I

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...