A 4-month-old boy is brought to the office by his parents due to progressive lethargy, poor feeding, fatigue, and increasing pallor for the past 4 weeks. Antenatal and birth histories are unremarkable. The patient's diet consists mainly of breast milk. Immunizations are current. Physical examination shows a webbed neck, cleft palate, mild hypertelorism, flat nasal bridge, and pale mucous membranes. The thumbs appear triphalangeal. Cardiac examination reveals tachycardia with a systolic ejection flow murmur. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 4 g/dL |
| Mean corpuscular volume | 104 µm3 |
| Reticulocytes | 0.4% |
| Platelets | 300,000/mm3 |
| Leukocytes | 7,500/mm3 |
| Blood type | A− |
Maternal blood type is O+. Which of the following is the most likely diagnosis in this patient?
Diamond-Blackfan anemia | |
Pathogenesis |
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Clinical findings |
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Laboratory findings |
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Treatment |
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This infant has macrocytic anemia, craniofacial anomalies, and triphalangeal thumbs consistent with Diamond-Blackfan anemia (DBA). DBA is caused by a congenital (inherited or sporadic) defect of erythroid progenitor cells, which leads to increased apoptosis of red blood cells, resulting in profound anemia. Most patients have other anomalies, such as short stature, cleft palate, and webbed neck.
DBA typically presents in infancy with progressive pallor and poor feeding due to anemia, as seen in this patient. The heart rate increases to meet oxygen demands, and a faint systolic ejection (flow) murmur may be heard on examination due to increased turbulence across the valves.
Laboratory testing differentiates the type of anemia. In contrast to Fanconi anemia (pancytopenic bone marrow failure), DBA is a pure red cell aplasia with reticulocytopenia and normal platelet and white blood cell counts (Choice B). Treatment mainly involves corticosteroids or transfusion therapy in refractory cases.
(Choice C) Idiopathic aplastic anemia is an acquired disease that results in pancytopenia, not pure red cell aplasia. Common triggers include chemicals (eg, benzene, phenylbutazone), drugs (eg, chloramphenicol, sulfonamides), infectious agents (eg, viral hepatitis), and ionizing radiation.
(Choice D) Although iron deficiency is a common cause of microcytic anemia in infancy, it is unlikely in this patient with an elevated mean corpuscular volume.
(Choice E) Hemolytic disease of the newborn due to Rh incompatibility occurs when an Rh-negative mother previously exposed to Rh-positive cells gives birth to an Rh-positive infant. The mother of this infant is Rh-positive (blood type O+) and the patient is Rh-negative (blood type A−); therefore, there is no risk of Rh incompatibility for the patient.
(Choice F) Wiskott-Aldrich syndrome is an X-linked disorder characterized by eczema, thrombocytopenia, and hypogammaglobulinemia, findings not present in this patient.
Educational objective:
Diamond-Blackfan anemia is a congenital, pure red cell aplasia characterized by macrocytic anemia and several congenital abnormalities, such as cleft palate, webbed neck, and triphalangeal thumbs.