A genetically determined disorder with features both of thalassaemia and congenital dyserythropoietic anaemia.

Abstract

Summary. What appears to be a hitherto unreported type of congenital anaemia has been found in six members of an Irish family. It is inherited in an autosomal dominant manner and is characterized by moderate anaemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphological abnormalities of the red cells (which are, however, well haemoglobinized), erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow, and in the peripheral blood after splenectomy. Potassium flux across the red cell membranes is increased and there is imbalanced globin chain synthesis with α‐chain production exceeding that of β‐chains by a factor of 2/1. Excess α‐chains in the bone marrow form a pool of similar magnitude to that observed in β‐thalassaemia heterozygotcs but the latter do not have red cell precursor inclusion bodies or the degree of ineffective erythropoiesis seen in the present cases. The most likely molecular mechanisms for this disorder are either an ‘overproduction abnormality’ of α‐chain synthesis, or a defect in cell division leading to increased amounts of genetic material per cell, a mechanism postulated recently as a basis for the unusual distribution of red cell enzyme levels in congenital dyserythropoietic anaemia.