congenital dyserythropoietic anemia type III

Congenital Dyserythropoietic Anemia Type III (CDA III)

Congenital dyserythropoietic anemia type III, also known as CDA III, is a rare and inherited blood disorder that affects the development of red blood cells. This condition is characterized by:

• Macrocytic anemia: A decrease in the number of red blood cells with increased size (macrocytosis) [3].
• Bone marrow erythroid hyperplasia: An increase in the production of red blood cells in the bone marrow, leading to a buildup of large multinucleated erythroblasts [3].
• Giant multinucleate erythroblasts: Abnormal red blood cell precursors with multiple nuclei are found in the bone marrow [3].

CDA III can manifest with mild to moderate anemia and is often associated with autosomal dominant inheritance, although new evidence suggests that it may also be passed on recessively [3]. This condition is extremely rare and has been observed in both familial and sporadic forms [5].

References:

• [1] Congenital dyserythropoietic anemia type III (CDA-III) is a group of very rare disorders characterized by similar bone marrow morphology. [7]
• [2] CDA type III is a rare autosomal dominant disorder characterized by macrocytic anemia, bone marrow erythroid hyperplasia and giant multinucleate erythroblasts. [3]
• [3] Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA (see this term) characterized by dyserythropoiesis, with big multinucleated erythroblasts in the bone marrow, and manifesting with mild to moderate anemia. [11]

Mild Signs and Symptoms

The signs and symptoms of Congenital Dyserythropoietic Anemia (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 [4]. This is a notable difference from other forms of CDA.

Common Symptoms

While symptoms can vary depending on the individual, some common signs and symptoms of CDA type III include:

• Mild anemia
• Jaundice (yellowing of the skin and eyes) that may be intermittent
• Congenital malformations, such as those involving the limbs, heart, kidneys, or hip [7]
• Iron overload, which can lead to organ damage over time

Other Possible Symptoms

In some cases, individuals with CDA type III may also experience:

• Fatigue and weakness
• Pale skin
• Larger-than-normal liver and spleen (hepatosplenomegaly)
• Suboptimal reticulocyte response for the degree of anemia [14]

It's essential to note that these symptoms can be mild and may not always be present. A proper diagnosis by a medical professional is necessary to confirm CDA type III.

References: [4] Sandstrom H, Wahlin A. Congenital dyserythropoietic anemia type III. Haematologica. 2000 Jul;85(7):753-7. [7] Tamary H, Dgany O. Congenital Dyserythropoietic Anemia Type I. 2009 Apr 21. [14] A Iolascon · 2013 · Cited by 155 — Patients usually present with anemia, jaundice, splenomegaly, and suboptimal reticulocyte response for the degree of anemia.

Diagnostic Tests for Congenital Dyserythropoietic Anemia Type III

Congenital dyserythropoietic anemia type III (CDA III) is a rare form of CDA, and its diagnosis can be challenging. However, several diagnostic tests can help identify this condition.

• Blood tests: A complete blood count (CBC), including mean corpuscular volume (MCV), red cell distribution width (RDW), and blood smear examination, are essential in diagnosing CDA III [11]. These tests can reveal mild to moderate anemia, macrocytosis in the peripheral blood, and giant multinucleated erythroblasts in the bone marrow.
• Bone marrow examination: This test is used to examine the bone marrow for distinct morphologic features, such as giant multinucleated erythroblasts [2].
• Serum bilirubin test: This test can determine the cause of jaundice and detect increased destruction of red blood cells [11].
• Body iron measurements: Laboratory testing, radiology/imaging, or biopsy of the liver can help measure body iron levels and diagnose secondary hemochromatosis [11].

Genetic Testing

In addition to these diagnostic tests, genetic testing can also be used to confirm a diagnosis of CDA III. Next-generation sequencing (NGS) testing allows for the detection of single nucleotide and copy number variants in genes associated with congenital dyserythropoietic anemia, including KIF23 [5].

References

[1] - 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.

[2] - Diagnosis is based on laboratory findings. The disorder is characterized by mild anaemia, macrocytosis in the peripheral blood, and giant multinucleated erythroblasts in the bone marrow.

[3] - The congenital dyserythropoietic anemias (CDAs) are a group of rare hereditary disorders characterized by congenital anemia, ineffective erythropoiesis with distinct morphologic features in bone marrow late erythroblasts, and the development of secondary hemochromatosis.

[4] - Congenital dyserythropoietic anemia type III (CDA III) is caused by a mutation in kinesin family member, KIF23.

[5] - Blood. 2013; 121 (23): 4791-4799.

[6] - CDA types I and II are inherited as autosomal recessive disorders, and type III disease is inherited as an autosomal dominant disorder.

[7] - Type I disease is caused by mutations of the CDAN1 gene. Codanin-1, the gene product, is a cell-cycle-regulated protein of currently unknown function.

[8] - Knowing when symptoms may have appeared can help medical providers find the correct diagnosis. Prenatal testing can also be used to diagnose CDA III in utero.

[9] - 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.

[10] - Congenital dyserythropoietic anemia type III is an extremely rare condition and has been observed in both familial and sporadic forms (see Table 64.2).

[11] - Diagnostic tests for congenital dyserythropoietic anemia. a. Complete blood count, including MCV, RDW, and blood smear examination:

Treatment Options for Congenital Dyserythropoietic Anemia Type III

Congenital dyserythropoietic anemia (CDA) type III is a rare inherited disorder characterized by ineffective erythropoiesis, leading to anemia and other complications. While there are no specific treatments that can cure CDA type III, various management strategies can help alleviate symptoms and prevent complications.

• Blood Transfusions: Regular blood transfusions may be necessary to manage anemia in patients with CDA type III.
• Iron Chelation Therapy: Iron overload is a common complication of CDA type III. Iron chelation therapy, such as deferoxamine or deferiprone, can help remove excess iron from the body and prevent organ damage.
• Bone Marrow Transplantation: In some cases, bone marrow transplantation may be considered to replace the faulty bone marrow with healthy stem cells.

Current Research and Future Directions

Research into CDA type III is ongoing, and new treatment options are being explored. For example, a study published in [9] found that a mutation in the KIF23/MKLP1 gene is responsible for CDA type III. This discovery may lead to the development of targeted therapies for this condition.

References

• [10]: Congenital dyserythropoietic anemia (CDA) type I (CDAI) is characterized by severe or moderate anemia, which is generally macrocytic, and relative reticulocytopenia and congenital anomalies, such as skeletal abnormalities, chest deformity, and short stature.
• [11]: Congenital Dyserythropoietic Anaemia (CDA) is a rare genetic disorder that affects the maturation of red blood cells. The disorder is classified into different types, with a prevalence ranging from 1 in 100,000 to 1 in 1,000,000 individuals.
• [13]: CDA types I and II are inherited as autosomal recessive disorders, and type III disease is inherited as an autosomal dominant disorder. Type I disease is caused by mutations of the CDAN1 gene.

Note: The references provided are based on the information available in the search results and may not be comprehensive or up-to-date.

Differential Diagnosis of Congenital Dyserythropoietic Anemia Type III

Congenital dyserythropoietic anemia type III (CDA III) is a rare and inherited disorder characterized by distinct morphologic abnormalities of marrow erythroblasts. The differential diagnosis of CDA III involves excluding other causes of macrocytosis, such as B12 deficiency, folic acid deficiency, or other acquired anemias known to be associated with dyserythropoiesis.

Exclusion of Other Causes

The diagnosis of CDA III should be considered following exclusion of other causes of macrocytosis, including:

• B12 deficiency
• Folic acid deficiency
• Other acquired anemias known to be associated with dyserythropoiesis

Key Diagnostic Features

CDA III is characterized by distinct morphologic abnormalities of marrow erythroblasts, which can include:

• Anisopoikilocytosis (unequal red blood cell sizes)
• Mature erythroblasts
• Basophilic stippling
• Poikilocytes (abnormal red blood cell shapes)

Genetic Mutations

Mutations in the KIF23 gene or the RACGAP1 gene can also determine a diagnosis of CDA III, type a or b, respectively.

Differential Diagnosis among CDAs

CDA III is one of three subtypes of congenital dyserythropoietic anemia (CDA), which are defined on the basis of bone marrow morphology. The differential diagnosis among CDAs involves considering the following:

• CDA I: characterized by severe or moderate anemia, relative reticulocytopenia, and congenital anomalies such as skeletal abnormalities
• CDA II: includes hemoglobinopathies, Diamond-Blackfan anemia, hereditary spherocytosis, and pyruvate kinase deficiency
• CDA III: characterized by distinct morphologic abnormalities of marrow erythroblasts

References

1. Nilsson-Sojka B, Sikström C, Holmgren G. Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25. Hum Mol Genet ...
2. Sandström H, Wahlin A. Congenital dyserythropoietic anemia type III.
3. Flow diagram for the differential diagnosis of CDAs and their related hereditary anemias.

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