obsolete congenital anemia

Obsolete Congenital Anemia: A Rare Blood Disorder

Obsolete congenital anemia refers to a rare and inherited blood disorder that affects the development of red blood cells in infants and children. This condition is characterized by a shortage of red blood cells, which prevents the blood from carrying an adequate supply of oxygen to the body's tissues.

Key Features:

• Inherited blood disorder affecting red blood cell development
• Shortage of red blood cells leading to inadequate oxygen supply
• Rare and congenital in nature (present at birth)
• Can be severe or moderate, with symptoms ranging from mild to life-threatening

Causes and Risk Factors:

• Genetic mutations affecting the production of red blood cells
• Inherited from parents who carry the mutated gene
• No known environmental risk factors or triggers

Symptoms and Diagnosis:

• Marked pallor (pale skin) and reticulocytopenia (low red blood cell count)
• Absence of red blood cell production in bone marrow
• Congenital anomalies, such as skeletal abnormalities, chest deformity, and short stature
• Severe or moderate anemia, which is generally macrocytic

Treatment and Management:

• No specific treatment available for obsolete congenital anemia
• Treatment focuses on managing symptoms and preventing complications
• Blood transfusions may be necessary to alleviate severe anemia

References:

• [1] Congenital dyserythropoietic anemias (CDA) type II is a rare hereditary chronic hemolytic anemia due to a defect in the SEC23B gene. [2]
• [3-5] Congenital erythropoietic porphyria (CEP), congenital hemolytic anemia, and other types of congenital anemias are distinct conditions with different causes and symptoms.
• [6] Excluding disorders of globin synthesis, rare anaemias include Diamond-Blackfan anaemia (DBA), congenital dyserythropoietic anaemias (CDA), and others.

Based on the provided context, it appears that there are several types of congenital dyserythropoietic anemia (CDA) with overlapping patterns of signs and symptoms.

Common Signs and Symptoms:

• Fatigue [9]
• Weakness [9]
• Pale skin [11]
• Jaundice (yellowing of the skin and eyes) [6, 13]
• Dark-colored urine [6]
• Shortness of breath [3]

Additional Signs and Symptoms for Specific Types:

• CDA type I:
  • Moderate to severe anemia [15]
  • Relative reticulocytopenia
  • Congenital anomalies (skeletal abnormalities, chest deformity, short stature) [15]
  • Distal limb anomalies (in approximately 10% of patients) [15]
• CDA type II and III:
  • Overlapping patterns of signs and symptoms with other types [11]

Other Complications:

• Ineffective red blood cell production leading to a decrease in the number of red blood cells in the body and less than normal quantity of hemoglobin [12, 14]
• Problems in various organs due to anemia and ineffective erythropoiesis [13]

It's worth noting that these signs and symptoms may vary depending on the specific type of CDA and individual patient presentation.

Based on the provided context, it appears that there are several diagnostic tests for congenital anemias that have been considered obsolete or abandoned due to various reasons.

• The acidified serum test (Ham test) was a historical laboratory test used in the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), but it has practically been abandoned as a diagnostic tool due to the need for multiple control samples [7].
• The Ham test is also mentioned in relation to congenital dyserythropoietic anemia (CDA) type I, where it was used to diagnose the condition, but its use has been discontinued [10].

On the other hand, there are several diagnostic tests that are still widely used for various types of congenital anemias:

• Flow cytometry-based eosin-5′-maleimide (EMA) binding test is most frequently employed for reliable diagnostics in conditions such as PNH and CDA [2, 5].
• Eosin-5-maleimide (EMA) flow cytometry or osmotic fragility (OF) testing are used to diagnose hereditary spherocytosis (HS) [12].
• Blood tests, imaging, and genetic tests are used to identify CDA, including blood tests such as full blood count, reticulocyte count, and haemolytic markers [4].

It's worth noting that the diagnostic approach for congenital anemias often involves a combination of these tests, depending on the specific condition being diagnosed.

References:

[2] by A Glenthøj · 2020 · Cited by 11 — The flow cytometry-based eosin-5′-maleimide (EMA) binding test is most frequently employed for reliable diagnostics. [4] by NBA Roy · 2022 · Cited by 20 — The traditional investigative pathway is to take a history and examination, full blood count, reticulocyte count, and haemolytic markers, before ... [5] by A Glenthøj · 2020 · Cited by 11 — The flow cytometry-based eosin-5′-maleimide (EMA) binding test is most frequently employed for reliable diagnostics. [7] by C Cantu · 2015 · Cited by 11 — The historical laboratory test and basis for its original namesake is the acidified serum test (Ham test) in which the defective erythroid ... [10] CDA type I (CDAI) is a rare congenital anemia characterized by normocytic or macrocytic anemia, with a positive family history and nonimmune spherocytic hemolytic anemia. [12] Diagnosis of HS is straightforward in the child with a positive family history and nonimmune spherocytic hemolytic anemia. PB smear shows variable numbers of spherocytes . Diagnostic testing includes eosin-5-maleimide (EMA) flow cytometry or osmotic fragility (OF) testing.

Treatment Options for Obsolete Congenital Anemias

While some congenital anemias may have been considered obsolete, advancements in medical research and treatment options have led to the development of new therapies that can effectively manage these conditions. Here are some drug treatments that were previously used or are still being explored for obsolete congenital anemias:

• Deferasirox: This once-daily oral chelator was approved by the FDA and EMA for use in transfusion-dependent anemias, including those caused by beta-thalassemia major [5]. Although its use may have been limited to specific cases, it remains a viable option for managing certain types of congenital anemia.
• Eltrombopag: This drug has shown efficacy in treating aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses reported in some patients [7]. While its use may be more focused on acquired forms of anemia, it could still be considered for obsolete congenital anemias.
• Luspatercept: This erythroid maturation agent has been approved for anemia in adults with beta thalassemia who require regular red blood cell transfusions [8]. Although its primary indication is for acquired forms of anemia, it may also be explored as a treatment option for obsolete congenital anemias.

Emerging Treatment Approaches

New research and advancements in medical science have led to the development of emerging treatment approaches that hold promise for obsolete congenital anemias:

• Gene therapies: Gene therapy or editing technologies are being explored for treating congenital forms of anemia, offering a potential cure for these conditions [14].
• Targeted therapies: Drugs targeting recently defined pathways in red blood cell production, iron metabolism, and fetal globin gene expression may also be investigated as treatment options for obsolete congenital anemias.

References

[5] P Manduzio · 2015 · Cited by 1 — Deferasirox is once-daily oral chelator approved by the Food and Drug Administration and the European Medicine Agency for use in transfusion-dependent anemias ...

[7] Eltrombopag is efficacious in a subset of patients with aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses.

[8] Aug 24, 2023 — Luspatercept, an erythroid maturation agent, is approved for anemia in adults with beta thalassemia who require regular red blood cell transfusions.

[14] Promising new treatment approaches include drugs that target recently defined pathways in red blood cell production, iron metabolism, and fetal globin gene expression, as well as gene therapies using improved viral vectors and newly developed genome editing technologies.

The differential diagnosis of obsolete congenital anemias involves considering various conditions that may present with similar symptoms to those of the condition in question.

Conditions to Consider

• Aplastic Anemia: A rare and life-threatening disorder characterized by hypocellular bone marrow, where the bone marrow cannot make enough new blood cells [3].
• Thymoma: A rare type of cancer that can cause anemia, particularly in adults [9].
• Congenital Dyserythropoietic Anemia (CDA): A rare form of anemia caused by mutations in two genes of unknown function: CDAN1 and CDAN2 [10].
• Hereditary Spherocytosis: A genetic disorder that affects the production of red blood cells, leading to anemia [4].

Other Considerations

• Autoimmune Diseases: Certain autoimmune conditions can cause anemia as a symptom [7].
• Chronic Myelomonocytic Leukemia: A rare type of leukemia that can present with anemia and other symptoms [7].
• Congenital Neutropenia: A rare genetic disorder characterized by low levels of neutrophils, which can lead to anemia [7].

Important Notes

• The differential diagnosis of congenital anemias can be challenging due to overlapping clinical features [4][6].
• It is essential to consider the age and presentation of the patient when making a differential diagnosis [8].

References:

[3] Aplastic Anemia: A rare life-threatening disorder with hypocellular bone marrow, where the bone marrow cannot make enough new blood cells. [4] Hereditary Spherocytosis: A genetic disorder that affects the production of red blood cells, leading to anemia. [6] Differential Diagnosis: It may be difficult in some cases to make a definite diagnosis when an infant presents only with anemia in the first weeks of life. [7] Diagnostic Considerations: Large granular lymphocyte leukemia, Autoimmune diseases, Chronic myelomonocytic leukemia, Congenital neutropenia. [8] In older children, the differential diagnosis includes various acquired causes of anemia such as transient erythroblastopenia of childhood. [9] The diagnosis of thymoma should be considered in adults, as it rarely occurs in children. DBA is diagnosed in adults more often than previously. [10] Congenital dyserythropoietic anemia type 1 (CDA-I) is a rare form of anemia caused by mutations in two genes of unknown function: CDAN1 and CDAN2.