HB MALMO [BETA-97(FG-4)HIS-]GLN] LEADING TO POLYCYTHEMIA IN A DUTCH FAMILY

We have examined six individuals from a two-generation Dutch family fo r a suspected hemoglobin (Hb) abnormality. The propositus presented wi th polycythemia and complained of persistent weakness, headache, and e pistaxis, All family members initially showed a normal Hb-electrophore tic pattern, but on isoelectric focusing, three of them displayed a fa st-moving band associated with high packed red cell volumes (PCV) and increased red blood cell count. The Hb mutant was analyzed at the DNA level by specific gene fragment amplification (PCR), followed by direc t DNA sequencing, and the mutation was confirmed by restric tion enzym e analysis, We found a C-->G transversion (CAC-->CAG) at codon 97 of t he beta-chain, which corresponded to the His-->Gln amino acid substitu tion previously described as Hb Malmo. We report here the clinical his tory of the patient, the effects of phlebotomy treatment, and the effe ct of subnormal iron conditions on the erythropoietic recovery after p hlebotomy. The mechanism responsible for the induction of the higher o xygen affinity is discussed, as are some aspects concerning the occurr ence, pathology, treatment, and the genetic risk of Hb variants with h igh O-2 affinity.