title: Haemolytic disease of the newborn and chronic anaemia induced by gamma beta thalassaemia in a Dutch family.
abstract: 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 recorded 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 adult had normal levels of Hbs A2 and F. Incorporation of [3H]leucine into the globin chains of two adults with this syndrome revealed a reduced beta-chain synthesis (beta/alpha ratio of 0 . 49 and 0 . 53, respectively). In the two infants available for this investigation, reduced gamma-chain production was found shortly after birth. In parallel with the switch from fetal to adult haemoglobin, the deficient gamma-chain production was replaced by a similar reduction of beta-chain synthesis. These results suggested, therefore, a combined deficiency of gamma- and beta-chain production. The normal levels of Hb A2 were compatible with a defective delta-chain synthesis as well. Analysis with restriction enzymes had shown previously a large deletion, comprising gamma and delta genes, in one of the chromosomes of the affected individuals. The same procedure had established that, in spite of the defective beta-chain production, the beta-globin structural gene is intact.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000745:Anemia, Hemolytic, Congenital / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004899:Erythroblastosis, Fetal / Q000209:etiology / Q000235:genetics*; D005260:Female; D005914:Globins / Q000096:biosynthesis; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics; D007231:Infant, Newborn; D007930:Leucine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D011247:Pregnancy; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D005914:Globins; D007930:Leucine