Snapshot A 1-month-old boy presents to the emergency department with poor feeding and lethargy. He was born to a 25-year-old mother at 38 weeks gestation via an uncomplicated spontaneous vaginal delivery. Physical examination is notable for conjunctival pallor, hypertelorism, and triphalangeal thumbs. Laboratory testing is remarkable for a macrocytic anemia, reticulocytopenia, and elevated erythrocyte adenosine deaminase activity and hemoglobin F. Introduction Overview a congenital impairment in erythrocyte formation that usually presents in infancy results in a pure red cell aplasia, which is an isolated anemia with reticulocytopenia characteristic findings include normochromic and usually macrocytic anemia reticulocytopenia decreased or absent erythroid precursors in the bone marrow elevated erythrocyte adenosine deaminase increased hemoglobin F presence of red blood cell i antigen Genetics inheritence pattern usually autosomal dominant mutations impaired ribosome synthesis Associated conditions increased risk for malignancies acute myelogenous leukemia myelodysplastic syndrome solid tumors (e.g., colon cancer) Epidemiology Demographics ~90% of patients are diagnosed within the first year of life ~35% of patients are diagnosed within the first month of life ETIOLOGY Pathophysiology believed to be due to genetic mutations impairing ribosome synthesis through unclear mechanisms, this results in activation of tumor protein p53, which impairs erythropoiesis Presentation Symptoms fatigue or lethargy poor feeding Physical exam congenital abnormalities (30-50% of patients) craniofacial abnormalities hypertelorism microcephaly ophthalmic abnormalities congenital cataracts or glaucoma neck anomalies scapular elevation Turner-like appearance vertebral fusion with flaring of the trapezius muscles cardiac and pulmonary anomalies atrial and ventricular septal defects thumb abrnormalities triphalangeal thumb Studies Serum labs isolated macrocytic anemia white blood cells and platelets are typically normal reticulocytopenia elevated hemoglobin F elevated erythrocyte adenosine deaminase activity Invasive studies bone marrow examination normal overall cellularity decreased or absent erythroid precursors Differential Transient erythroblastopenia of childhood differentiating factors an acquired anemia typically secondary to a viral illness absent congenital anomalies normal erythrocyte adenosine deaminase activity absent red blood cell I antigen Treatment Medical corticosteroids indication first-line treatment option that is preferably given in infants at least 6-12 months of age comments reticulocytes typically begin to appear and increase within 1-2 weeks blood transfusion indication first-line treatment in patients who are not responding to corticosteroids or are not candidates for corticosteroids Complications Iron overload from blood transfusions Hyperglycemia from corticosteroids Anemia Prognosis 40% of patients become steroid dependent 40% of patients are blood transfusion dependent Spontaneous remission has been reports in ~25% of patients