Congenital dyserythropoietic anemia (CDA) type 1 is an inherited blood disorder 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. CDA type I usually results from mutations in the CDAN1 (about 90% of the cases) and C150RF41 genes (about 1% of the cases). In about 9% of the cases no cause can be identified. It is inherited in an autosomal recessive pattern. Treatment involves medication such as interferon, and sometimes bone marrow transplant.

CDA type I usually results from mutations in the CDAN1 gene. Little is known about the function of this gene, and it is unclear how mutations cause the characteristic features of CDA type I. Some people with this condition do not have identified mutations in the CDAN1 gene, leading researchers to believe that mutations in at least one other gene can also cause this form of the disorder.

CDA type II is caused by mutations in the SEC23B gene. This gene provides instructions for making a protein that is involved in the transport of other proteins within cells. During the development of red blood cells, this protein may help ensure that proteins are transported to the areas where they are needed. Researchers are working to determine how mutations in the SEC23B gene lead to the signs and symptoms of CDA type II.

The genetic cause of CDA type III has not been identified. It likely results from mutations in a gene located on the long arm of chromosome 15 at a position designated 15q22. Researchers continue to search for the specific gene associated with this form of the condition.

The genetic changes responsible for CDA disrupt the normal development of red blood cells, a process called erythropoiesis. The term "dyserythropoietic" in the name of this condition means abnormal red blood cell formation. In people with CDA, immature red blood cells called erythroblasts are unusually shaped and have other abnormalities (such as extra nuclei). These abnormal erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including hepatosplenomegaly and an abnormal buildup of iron.

Normal Function

The CDAN1 gene provides instructions for making a protein called codanin-1. Although this protein is active in cells throughout the body, very little is known about its function.

A recent study suggests that codanin-1 is associated with a form of DNA called heterochromatin. Heterochromatin is densely packed DNA that contains few functional genes, but it plays an important role in maintaining the structure of the nucleus (where most of the cell's DNA is located).

Researchers speculate that codanin-1 may be involved in the formation of red blood cells, a process called erythropoiesis. Specifically, this protein may play a key role in the organization of heterochromatin during the division of these developing cells.

Health Conditions Related to Genetic Changes

Congenital dyserythropoietic anemia

More than 30 mutations in the CDAN1 gene have been identified in people with congenital dyserythropoietic anemia (CDA) type I. Most of these mutations change single protein building blocks (amino acids) in the codanin-1 protein. The CDAN1 mutations that cause CDA type I likely reduce the function of codanin-1. However, researchers suspect that these mutations do not completely eliminate the function of the protein, which appears to be essential for life.

It is unclear how CDAN1 mutations cause the characteristic features of CDA type I. A shortage of functional codanin-1 somehow disrupts the normal development of red blood cells. In people with CDA type I, immature red blood cells called erythroblasts are large, unusually shaped, and have an abnormally formed nucleus. These defective erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including an enlarged liver and spleen (hepatosplenomegaly) and an abnormal buildup of iron that can damage the body's organs.

Other Names for This Gene

• CDA-I
• CDA1
• CDAI
• CDAN1_HUMAN
• codanin
• congenital dyserythropoietic anemia, type I
• DLT
• PRO1295

Genomic Location

Normal Function

The SEC23B gene provides instructions for making one component of a large group of interacting proteins called coat protein complex II (COPII). COPII is involved in the formation of vesicles, which are small sac-like structures that transport proteins and other materials within cells. Specifically, COPII triggers the formation of vesicles in a cellular structure called the endoplasmic reticulum (ER), which is involved in protein processing and transport. These COPII vesicles carry proteins that are destined to be exported out of cells (secreted).

The SEC23B protein is very similar to the protein produced from a related gene, SEC23A. These proteins are both components of COPII, and they appear to have overlapping functions. In most types of cells, if one of these proteins is missing, the other may be able to compensate for the loss. However, research indicates that the SEC23B protein may have a unique function in developing red blood cells (erythroblasts).

Health Conditions Related to Genetic Changes

Congenital dyserythropoietic anemia

At least 20 mutations in the SEC23B gene have been identified in people with congenital dyserythropoietic anemia (CDA) type II. Most of these mutations change single protein building blocks (amino acids) in the SEC23B protein. Other mutations delete genetic material from the SEC23B gene or alter the way the gene's instructions are used to make the SEC23B protein. The mutations responsible for CDA type II likely disrupt the function of the SEC23B protein. However, researchers suspect that these mutations do not completely eliminate the function of the protein, which appears to be essential for life.

It is unclear how SEC23B mutations cause the characteristic features of CDA type II. The abnormal SEC23B protein leads to the production of erythroblasts that are unusually shaped and may have extra nuclei. These defective erythroblasts cannot develop into functional mature red blood cells. The resulting shortage of healthy red blood cells leads to the characteristic signs and symptoms of anemia, as well as complications including an enlarged liver and spleen (hepatosplenomegaly) and an abnormal buildup of iron that can damage the body's organs.

Cowden syndrome

MedlinePlus Genetics provides information about Cowden syndrome

Other Names for This Gene

• CDA-II
• CDAII
• HEMPAS
• SC23B_HUMAN
• Sec23 homolog B
• Sec23 homolog B (S. cerevisiae)
• Sec23 homolog B, COPII coat complex component
• SEC23-like protein B
• SEC23-related protein B
• transport protein SEC23B

Genomic Location

• Anemia: Which is moderate in most cases
• Jaundice
• Iron overload (hemochromatosis): Increased iron absorption may result in heart problems such as congestive heart failure and altered heart rhythm (arrhythmia), as well as liver disease (cirrhosis) and diabetes.
• Splenomegaly and/or hepatomegaly: May be absent in infants or young children, but develop later with age.
• Gallstones: May be present in some affected people.
• Skeletal findings: Specifically in the fingers and toes.
• Eye problems resulting in poor vision