Diamond-Blackfan anemia 2

Diamond-Blackfan Anemia: A Rare Genetic Disorder

Diamond-Blackfan anemia (DBA) is a rare genetic disorder that primarily affects the bone marrow. People with this condition often also have physical abnormalities affecting various parts of the body.

• Causes: DBA can be caused by mutations in one of many genes, including the RPL5, RPL11, RPL35A, RPS10, RPS17, RPS19, RPS24, and RPS26 genes. These genetic mutations affect the production of red blood cells in the bone marrow.
• Symptoms: People with DBA often experience a low red blood cell count (anemia), which can lead to fatigue, weakness, and shortness of breath. They may also have physical abnormalities such as congenital malformations affecting various parts of the body.

According to [2], DBA is characterized by mutations in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified. A mutation in the RPS19 gene is the cause of DBA in about 25% of patients.

DBA is a rare and complex condition that requires proper diagnosis and treatment to manage its symptoms and prevent complications.

Common Signs and Symptoms of Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a rare blood disorder that affects people's bone marrow and disrupts red blood cell production. The signs and symptoms of DBA can vary from person to person, but here are some common ones:

• Pale skin: People with DBA often have pale skin due to the lack of red blood cells.
• Sleepiness: Fatigue is a common symptom of DBA, which can make people feel tired or sleepy.
• Irritability: Some individuals with DBA may become irritable or restless due to the anemia.
• Rapid heartbeat: A rapid heartbeat (tachycardia) is another sign of DBA.
• Poor appetite: People with DBA often have a poor appetite, which can lead to weight loss and other complications.

According to [3], approximately ninety percent of affected patients exhibit these symptoms. It's essential to note that some people may not show any signs or symptoms at all, especially if they are mildly affected.

In addition to these common symptoms, DBA can also cause:

• Low birth weight: Babies born with DBA may have low birth weight or delayed growth.
• Distinct facial features: Some individuals with DBA may have distinct facial features, such as a small jaw or nose.
• Thumbs that are missing or have a deformity: In some cases, people with DBA may be born with thumbs that are missing or have a deformity.

It's crucial to seek medical attention if you suspect someone has DBA. A diagnosis can be made through blood sample testing and bone marrow testing, as mentioned in [14].

Diagnostic Tests for Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) can be diagnosed through various tests that help identify the condition and rule out other possible causes. Here are some of the diagnostic tests used to diagnose DBA:

• Complete Blood Count (CBC): A CBC test measures the levels of different blood cells, including red blood cells, white blood cells, and platelets. In children with DBA, a low number of red blood cells is typically observed, while white blood cell and platelet counts are usually normal [3].
• Blood tests for anemia: Blood tests can help diagnose anemia, which is a hallmark of DBA. Hemoglobin and hematocrit levels are often measured to determine the severity of anemia [6].
• Bone marrow tests: Bone marrow aspiration and biopsy may be performed to evaluate the bone marrow's ability to produce red blood cells. In children with DBA, the bone marrow may appear normal or show a paucity of red cell precursors [7].
• Blood tests for Diamond-Blackfan gene: Genetic testing can help identify mutations in the RPS19, RPS17, and other genes associated with DBA [4].

Early Diagnosis

DBA is often diagnosed early in life, typically before age 2 years. In fact, diagnosis usually occurs between 2-3 months of age, and in 95% of cases, children are diagnosed before age 2 years [15]. Early diagnosis is crucial for prompt treatment and management of the condition.

References

[3] Your doctor can use several tests to find out if your child has DBA, usually before age 1. Children with DBA have a low number of red blood cells, but normal white blood cells and platelets. Your doctor will likely take a complete blood count, or CBC.

[4] by A Vlachos · 2008 · Cited by 535 — Routine cytogenetic analysis is usually normal. The genetic basis of DBA is heterogeneous and approximately 50% of patients are heterozygous for RPS17, RPS19, ...

[6] It is diagnosed based on the signs and symptoms, and on the results of blood and bone marrow testing. Anemia is diagnosed with: Hemoglobin and hematocrit.

[7] How is Diamond-Blackfan anemia in children diagnosed? · Blood tests · Bone marrow aspiration and biopsy may be performed to evaluate the bone marrow's ability to produce red blood cells.

[15] According to a 2020 article, DBA is present from birth, and doctors may diagnose the disorder at around 2–3 months. In 95% of cases, doctors diagnose children before age 2 years.

Treatment Options for Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome, and treatment options are limited. However, various medications have been used to manage the condition.

• Corticosteroids: These are the first-line treatment for DBA, with 82% of patients initially responding to steroids [4]. The starting dose is typically 2 mg/kg per day, usually as prednisone or prednisolone, for a maximum trial of 4 weeks [3].
• Blood Transfusions: Patients may require chronic blood transfusions due to long-term side effects of corticosteroids. Concurrent iron chelation therapy is often necessary to manage iron overload [11].
• Stem Cell Transplant: In some cases, stem cell transplantation may be considered as a treatment option for DBA.
• Other Medications: Research has explored the use of other medications, such as trifluoperazine and fenofibrate, but their effectiveness is still being studied.

Important Considerations

It's essential to note that patients with DBA often require long-term management due to the chronic nature of the condition. Regular monitoring for side effects and complications is crucial when using corticosteroids or other medications.

References:

[3] A Vlachos · 2010 · Cited by 261 [4] According to the Diamond Blackfan Anemia Registry (DBAR) [11] Corticosteroids are the first-line treatment of Diamond Blackfan anemia. However, due to long-term side effects of corticosteroids, patients with DBA often require chronic blood transfusions and concurrent iron chelation therapy. [3] Our corticosteroid starting dose is 2 mg/kg per day, usually as prednisone or prednisolone, for a maximum trial of 4 weeks.

Differential Diagnosis of Diamond-Blackfan Anemia

Diamond-Blackfan anemia (DBA) is a rare congenital erythroid aplasia that can be challenging to diagnose due to its similarity with other blood disorders. The differential diagnosis for DBA includes several conditions that present with similar symptoms, such as:

• Transient Erythroblastopenia: This condition is characterized by a temporary decrease in the production of red blood cells, which can lead to anemia. It is often seen in children and can be distinguished from DBA by its transient nature.
• Chronic Parvovirus B19 Infection: This viral infection can cause a decrease in red blood cell production, leading to anemia. However, it is typically associated with other symptoms such as fever, rash, and joint pain.
• Other Congenital Anemias: DBA should also be differentiated from other congenital anemias, including Fanconi anemia, Shwachman-Diamond syndrome, and congenital dyserythropoietic anemia.

Key Points to Consider

• The differential diagnosis for DBA is broad and includes several conditions that can present with similar symptoms.
• Transient erythroblastopenia, chronic parvovirus B19 infection, and other congenital anemias should be considered in the differential diagnosis of DBA.
• A thorough medical history, physical examination, and laboratory tests are essential to differentiate DBA from these conditions.

References

• [3] Table 3. Differential Diagnosis of Diamond-Blackfan Anemia: Genetic Conditions with Bone Marrow Failure.
• [5] The differential diagnosis should include transient erythroblastopenia (see this term), chronic parvovirus B19 infection, and other congenital anemias.
• [10] Differential Diagnosis. Diamond Blackfan anemia has a unique quantitative defect in erythropoiesis rather than hematopoiesis, ...