HEMOGLOBIN F-CINCINNATI, ALPHA(2)(G)GAMMA(2) 41(C7) PHE-]SER IN A NEWBORN WITH CYANOSIS

A term infant presented with mid cyanosis without evidence of hypoxla. Cardiopulmonary disease, polycythemia, and methemoglobinemia were exc luded. Standard hemoglobin electrophoresis, including isoelectric focu sing, were normal. However, by reverse-phase C-4 HPLC, an abnormal glo bin chain was detected. Analysis of tryptic peptides and amino acid se quence showed that the patient had an amino acid substitution Phe-->Se r at residue 41(C7) in the (G) gamma chain. This was confirmed by DNA sequencing that demonstrated a point mutation at the expected site in exon 2 of the (G) gamma gene, accounting for the appropriate change in the codon. This substitution, hemoglobin F-Cincinnati, alpha(2) gamma (2) 41(C7) Phe-->Ser, not previously described, presumably decreased o xygen affinity of the hemoglobin. This substitution is very near the h eme group and the alpha(1) beta(2) interface and, hence, in a crucial area of the globin chain. Abnormalities of gamma globin chains tend to be overlooked due to their transient presence and trivial clinical sy mptomatology, or due to ''in utero'' selection when physiologically ab normal. Mutant hemoglobins with altered oxygen affinity should be incl uded in the differential diagnosis of newborns presenting with cyanosi s, in whom all common causes have been excluded. (C) 1995 Wiley-Liss, Inc.