The association of Hb Khartoum [β124(H2)Pro→Arg] with γ+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta 124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma(+)-thalassemia point mutations, one affecting both (A)gamma and (G)gamma genes at IVS-II-115 (A-->G), and one affecting the (G)gamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the ye-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma(+)-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma(+)-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma(+)-thalassemia is responsible for neonatal hemolytic anemia in this family.