Chapter 7: Congenital Dyserythropoietic Anemias

INTRODUCTION

• Congenital dyserythropoietic anemias (CDAs) are a heterogeneous group of disorders characterized by anemia, ineffective erythropoiesis with specific morphological alterations of erythroid precursors in the marrow, and iron overload.

• Although rare, uncovering the molecular basis of CDA has helped unravel novel aspects of the cell biology of erythropoiesis.

• Three classical types of CDA have been distinguished. However, some patients with phenotype of CDA do not fit into any of these categories.

CDA TYPE I

Clinical and Laboratory Features

• The condition presents in infancy or adolescence.

• Autosomal recessive inheritance is caused by mutations in the CDAN1 gene, encoding codanin-1, a cell cycle–regulated protein involved in the histone assembly; homozygosity is often associated with consanguinity. In a number of patients, only one or no CDAN1 mutated allele is identified; other causative genes, such as C15ORF41, are suspected.

• Moderately severe macrocytic anemia (approximately 9.0 g/dL) occurs.

• Hepatomegaly and cholelithiasis are common.

• Splenomegaly increases with age.

• Specific morphologic findings of CDA type I are summarized in Table 7–1 and exemplified in Figure 7–1.

• Dysmorphic skeletal features may be present, typically affecting hands and feet. Less common are small stature, almond-shaped blue eyes, hypertelorism, and micrognathia.

Differential Diagnosis

• The condition may be confused with the thalassemias (see Chap. 15).

• Megaloblastoid marrow morphology may suggest folic acid or vitamin B₁₂ deficiency (see Chap. 8).

Treatment

• Severe forms may present with ...