Transient Erythroblastopenia of Childhood vs Diamond Blackfan Anemia

Transient erythroblastopenia of childhood (TEC)

• the most common form of pure red blood cell aplasia in children
• acquired disorder occurs in previously healthy children
• pathophysiology is not understood, although many have presumed a viral etiology.
• Presentation between 1 and 3 years of age. Only 20% of TEC patients are younger than 1 year of age
• average hemoglobin at presentation is 5.7 g/dL (57 g/L).
• White blood cell and platelet counts are usually normal, but neutropenia is common.
• The anemia is normocytic and normochromic, and hemoglobin F levels are normal for age.
• Severe erythroid hypoplasia is evident in the bone marrow unless spontaneous recovery already is occurring, in which case erythroid hyperplasia precedes the reticulocytosis and recovery.
• All patients recover, with 60% requiring a transfusion for support until recovery.
• The recommendation is to observe patients and provide transfusion if there is a risk of cardiovascular compromise.  No other therapy is indicated.

TEC must be distinguished from Diamond-Blackfan anemia (DBA), a much more serious disorder.

Diamond-Blackfan anemia, or congenital hypoplastic anemia, is associated with physical abnormalities in approximately 25% of patients. Anomalies include a typical facies, micrognathia, flattening of the thenar eminences, and triphalangeal thumbs.

• aka Congenital Hypoplastic Anemia
• Both dominant and autosomal recessive, but 75% of cases are sporadic,
• A defect of the erythroid stem cell is most likely responsible for the disorder.
• Pallor usually is recognized at or soon after birth.
• 90% of children who have DBA are diagnosed by 1 year
• Approximately 25% of patients demonstrate physical anomalies, most commonly of the head and face.
• Hemoglobin levels average 4 g/dL (40 g/L) at diagnosis.
• Macrocytosis is frequent, and reticulocytes are decreased or absent.
• White blood cell counts are usually normal.
• Although platelet counts also generally are normal, thrombocytopenia may be noted at some point in 25% of patients.
• more "fetal-like" erythropoiesis: Elevated hemoglobin F, increased titers of red blood cell membrane "i" antigen, and higher MCV
• Bone marrow examination usually reveals erythroid hypoplasia.
• Red blood cell adenosine deaminase levels often are elevated.
• Unlike TEC, DBA does not remit spontaneously.
• Corticosteroids are useful.
• Fewer than 5% of patients respond rapidly and enter a steroid-independent remission
• up to 60% respond but remain steroid-dependent
• up to 20% eventually may be able to discontinue steroids
• fewer than 5% respond only to very large doses of steroids and become transfusion-dependent
• 30% to 40% fail to respond to corticosteroids.
• Approximately 15% of patients die.
• Bone marrow  transplantation can be effective.
• appears to be a small but increased risk of leukemia among children who have DBA.

One feature that helps to distinguish TEC from DBA is age, with only 20% of TEC patients being younger than 1 year of age and more than 90% of children who have DBA being diagnosed by 1 year. The presence of associated physical anomalies, elevated hemoglobin F, macrocytosis, increased red blood cell "i" antigen, and elevated red blood cell adenosine deaminase support a diagnosis of DBA.

Other forms of pure red blood cell aplasia in children are very rare.

• The anemia of chronic disease usually is associated with an obvious underlying disorder and rarely is profound.
• Fanconi anemia seldom presents with anemia in the first year, and usually physical anomalies, pancytopenia, and macrocytosis are evident.
• Severe iron deficiency would be expected to be microcytic.

Several other disorders are associated with skeletal anomalies and hematologic disease.

• Fanconi's Anemia (no thumb or radius)
• Schwachman-Diamond Syndrome (pancreas)
• Dyskeratosis Congenita (skin and nail changes)
• TAR syndrome (thrombocytopenia, absent radius, thumbs present)
• Diamond-Blackfan Anemia (RBC hypoplasia)
• Bloom syndrome (predisp to leukemia, malignancies)
• Other rare disorders associated with both skeletal anomalies and hematologic disorders include
  • familial aplastic anemia syndromes
  • cartilage-hair hypoplasia
  • Dubowitz syndrome
  • Seckel syndrome
  • Poland syndrome
• Acquired disorders also may be associated with both hematologic and skeletal abnormalities. Children who have newly diagnosed acute lymphoblastic leukemia often present with bone pain and generalized radiologic signs, but they do not have congenital abnormalities.

References:
Alter BP, Young NS. The bone marrow failure syndromes. In: Nathan DG,
Orkin SH, Oski FA, Ginsburg D, eds. Nathan and Oski's Hematology of
Infancy and Childhood. 5th ed. Philadelphia, Pa: WB Saunders Co; 1998:
286-301
Freedman MH. Inherited forms of bone marrow failure. In: Hoffman R,
Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and
Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:260-297