Chapter 4: Pure Red Cell Aplasia

DEFINITION

• Pure red cell aplasia describes isolated anemia secondary to failure of erythropoiesis. Cardinal findings are a low hemoglobin level combined with reticulocytopenia and absent or extremely infrequent marrow erythroid precursors.

CLASSIFICATION

• See Table 4–1.

CONSTITUTIONAL PURE RED CELL APLASIA (DIAMOND-BLACKFAN ANEMIA)

• This form of pure red cell aplasia, which occurs in infancy and early childhood, is also known as either Diamond-Blackfan or Blackfan-Diamond anemia.

• It has an estimated annual incidence of five cases per one million live births.

• Inheritance is usually autosomal dominant or occasionally autosomal recessive if a familial pattern. Sporadic cases are most frequent.

• In this disease of abnormal ribosomal biogenesis, a genetic etiology can be identified in approximately 65% of cases. Mutations involve the RPS19 gene in approximately 25% of cases; several other genes that regulate ribosome assembly have been implicated.

• Pathophysiology is unclear.

Clinical Features

• Presenting symptoms include pallor, listlessness, poor appetite, and failure to thrive.

• One-third of patients are diagnosed at birth or in the early neonatal period, but the disease may appear at any time into adulthood.

• Physical abnormalities occur in one-third of patients (eg, craniofacial dysmorphism, short stature, abnormalities of the thumb, web neck, and urogenital and cardiac abnormalities).

• Disease may progress to severe anemia, with cardiac failure, dyspnea, and hepatosplenomegaly.

Laboratory Features

• Absolute severe reticulocytopenia occurs in all cases.

• Normocytic, occasionally macrocytic, normochromic anemia is found.

• Leukocyte count is normal or slightly decreased. Neutropenia may develop over several years.

• Platelet count is normal or mildly increased.

• Marrow is cellular but with marked erythroid hypoplasia. The few erythroid cells present may have megaloblastic changes. Other marrow cells are normal.

• Serum iron levels are elevated and transferrin saturation is increased.

• Erythropoietin levels are elevated.

• Erythrocyte adenosine deaminase activity is elevated in 75% of patients.

Differential Diagnosis

• Characteristic triad includes anemia, reticulocytopenia, and paucity/absence of marrow erythroid precursors. Findings are supplemented by increased erythrocyte adenosine deaminase activity and RPS19 gene mutations.

• Fanconi anemia can be excluded by cytogenetic and gene mutation analyses.

• Transient erythroblastopenia of childhood is established ...