Chapter 7: Congenital Dyserythropoietic Anemias

INTRODUCTION

• Congenital dyserythropoietic anemias (CDA) are a heterogeneous group of disorders characterized by anemia, the presence of multinuclear erythroid precursors in the marrow, ineffective erythropoiesis, and iron overload.

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

• Three types of CDA have been distinguished. In addition, a number of patients with forms of congenital dyserythropoietic anemia that do not fit these categories have been described.

CDA TYPE I

Clinical and Laboratory Features

• Presents in infancy or adolescence.

• Autosomal recessive inheritance, caused by mutations of the CDAN1 gene (codanin-1), encoding a cell-cycle-regulated protein of yet unknown function; homozygosity is often associated with consanguinity. In a number of patients, only one CDAN1 allele is identified with a mutation; other causative genes suspected because in rare CDA I families, no mutations of the CDAN1 gene found.

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

• 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 Fig. 7–1.

• Dysmorphologic features may be present, the most common involve the bones of the hand and the foot. Other, less common features are small stature, almond-shaped blue eyes, hypertelorism (increased distance between two body parts or organs), and micrognathism.