Clinical Features of Hemoglobin CHarlem, A New Sickling Hemoglobin Variant

Hemoglobin CHarlem (Hb CH) is a new hemoglobin variant that migrates near the position of Hb C on electrophoresis at pH 8.6 and is associated with erythrocyte sickling and gelation and relative insolubility of the hemolysate upon deoxygenation. Its structure was shown previously to be α2 A β2 6 Glu → Val, 73 Asp → Asn (Glu = glutamic acid; Val = valine; Asp = aspartic acid; Asn = asparagine); amino acid substitutions occur in two residues of each beta-polypeptide chain, one identical to that in Hb S (β6 Val) and one not previously observed in a hemoglobin variant (β73 Asn). Occasional target cells on peripheral smears and erythrocyte sickling are the only hematological abnormalities consistently found in Hb CH heterozygotes. The only associated clinical abnormality is a renal concentrating defect, found in each of seven affected family members. The propositus had a modestly reduced or low-normal capacity to reabsorb solute-free water during osmotic diuresis. Erythrocytes from persons with Hb CH trait show some sickling in hypertonic saline without deoxygenation; this finding and the renal functional abnormalities are similar to those seen in persons with sickle cell trait and suggest that the renal concentrating defects in the two disorders have similar pathogeneses. Clinical similarities between heterozygosity for Hb CH and Hb S are consistent with previous findings in gelation experiments; although purified deoxyhemoglobin CH requires a much higher concentration to gel than does deoxyhemoglobin S, each interacts similarly with Hb A. Thus Hb CH-trait and sickle cell-trait erythrocytes might sickle under similar physiological circumstances.