Haemolytic Disease of the Newborn and Chronic Anaemia Induced by γβ Thalassaemia in a Dutch Family

S ummary. Severe haemolytic anaemia with hyperbilirubinaemia and erythroblastaemia was observed in nine newborn infants belonging to one large family. One infant was still‐born, two died shortly after birth, five recovered after receiving one or more exchange transfusions and one improved without transfusional therapy. In four out of six newborns whose bilirubin levels were determined, a mixed hyperbilirubinaemia was found with high concentrations of both free and conjugated bilirubin. At the end of the first year of life the surviving children, although in satisfactory general condition, showed a mild microcytic hypochromic anaemia with decreased red cell osmotic fragility and morphological abnormalities of the erythrocytes consisting of microcytosis, anisopoikilocytosis and target cells. The serum iron levels were normal. The same haematological picture was also present in those parents of the affected children that are members of this family; these adults had normal levels of Hbs A 2 and F. Incorporation of [3H]leucine into the globin chains of two adults with this syndrome revealed a reduced β‐chain synthesis (β/α ratio of 0.49 and 0.53, respectively). In the two infants available for this investigation, reduced γ‐chain production was found shortly after birth. In parallel with the switch from fetal to adult haemoglobin, the deficient γ‐chain production was replaced by a similar reduction of β‐chain synthesis. These results suggested, therefore, a combined deficiency of γ and β‐chain production. The normal levels of Hb A 2 were compatible with a defective δ‐chain synthesis as well. Analysis with restriction enzymes had shown previously a large deletion, comprising γ and δ genes, in one of the chromosomes of the affected individuals. The same procedure had established that, in spite of the defective β‐chain production, the β‐globin structural gene is intact.