Congenital dyserythropoietic anemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Congenital dyserythropoietic anemia (CDA) is a rare group of inherited blood disorders that affects the development of red blood cells. In people with CDA, immature red blood cells do not develop into normal, mature cells. As a result, affected individuals have a significant reduction in the number of functional red blood cells (anemia). The term "dyserythropoietic" refers to the abnormal red blood cell shape that occurs in people with this condition. People with CDA typically have mild to moderate anemia. In some cases, affected individuals have severe anemia that may require frequent blood transfusions to replenish the supply of red blood cells.

The signs and symptoms of CDA can include tiredness (fatigue), weakness, yellowing of the skin and eyes (jaundice), and an enlarged liver and spleen (hepatosplenomegaly). CDA also causes the body to absorb too much iron (iron overload), which can damage tissues and organs.

There are multiple types of CDA. Each type has a different genetic cause and distinct but overlapping patterns of signs and symptoms.

CDA type I is characterized by moderate to severe anemia that typically begins in childhood or adolescence, although the condition can be detected before birth in some cases. In addition to the signs and symptoms common to all types of CDA, individuals with CDA type I can have skeletal issues, including short stature or abnormalities of the fingers or toes.

The anemia associated with CDA type II can range from mild to severe, and it usually develops in adolescence or early adulthood. Individuals with CDA type II may develop hard deposits in the gallbladder called gallstones in addition to the usual signs and symptoms of CDA.

CDA type III can result in anemia that ranges from mild to severe, depending on the genetic cause, and typically begins in infancy or childhood. Some people with CDA type III do not receive a diagnosis until later in life because they have very mild symptoms. In some cases, individuals with CDA type III develop a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma). Some people with CDA type III have eye abnormalities that can cause vision impairment.

CDA type IV is characterized by moderate to severe anemia that typically develops early in life, although the condition can be detected before birth in some cases. Affected individuals can have extensive swelling caused by fluid accumulation before birth (hydrops fetalis). In addition to the signs and symptoms that are common to all types of CDA, individuals with CDA type IV often have short stature.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in multiple genes have been found to cause CDA. Variants in these genes cause CDA by disrupting the normal development of red blood cells (erythropoiesis). In people with CDA, immature red blood cells called erythroblasts are unusually shaped and have other abnormalities. These abnormal erythroblasts either develop into irregular red blood cells or do not develop at all. Irregular red blood cells are quickly removed from circulation. The cells go to the spleen for destruction, and the resulting iron goes to the liver to be processed. The overall shortage of healthy red blood cells leads to the characteristic signs and symptoms of CDA, including anemia, hepatosplenomegaly, and iron overload.

CDA type I is caused by variants in the CDAN1 or CDIN1 gene. These genes provide instructions for making proteins that can attach (bind) to each other and play roles in cell division and erythropoiesis. In at least 10 percent of cases of CDA type I, the cause of the condition is unknown.

CDA type II is caused by variants in the SEC23B gene. This gene provides instructions for making a protein that is involved in the transport of other proteins within cells. During erythropoiesis, this protein may help ensure that proteins are transported to the areas where they are needed.

CDA type III is caused by variants in either the KIF23 or RACGAP1 gene. The KIF23 and RACGAP1 genes provides instructions for making proteins that can bind to each other to form a complex. This complex plays a critical role in the step of cell division in which the dividing cells separate from one another (cytokinesis). The complex also appears to be particularly important in the bone marrow where red blood cells grow and divide (proliferate).

CDA type IV is caused by variants in the KLF1 gene. This gene provides instructions for making a protein that regulates the activity of genes involved in erythropoiesis.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

The inheritance pattern of CDA depends on the type of the disorder. CDA types I and II are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition. When CDA type III is caused by variants in the RACGAP1 gene, it is also inherited in an autosomal recessive pattern.

CDA type IV appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. When CDA type III is caused by variants in the KIF23 gene, it is also inherited in an autosomal dominant pattern.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

CDA is a rare disorder, though the exact prevalence of CDA is unknown. CDA type II is the most common form of the disorder. Because CDA is rare and the signs and symptoms may be mild or overlap with those of other disorders, many cases likely remain undiagnosed or are incorrectly diagnosed as other disorders.

Which doctor should you see?

The suggested department for discussing Congenital dyserythropoietic anemia is Haematology, with a haematologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which blood-cell, marrow, bleeding or clotting finding matters most?
• Does the diagnosis need confirmation or a more precise subtype?
• Which symptoms or laboratory changes should trigger earlier review?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Congenital dyserythropoietic anemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.