Hb Buffalo [alpha89(FG1)His-->Gln (alpha1)], observed solely and in the presence of an Hb S [beta6(A3)Glu-->Val] heterozygosity.
The hemoglobin (Hb) pattern of a 32-year-old Somali male living in The Netherlands, during routine diabetes mellitus monitoring, showed two more peaks in addition to the characteristic heterozygous Hb A/S pattern. A major peak of 15% faster than Hb A, and a minor one of 10.8%, overlapping Hb A2 and the glycated Hb S1c fraction were present. The patient was not anemic or microcytic but had a low haptoglobin level, possibly indicating a slightly elevated red blood cell (RBC) turnover. Hb S was confirmed by a sickle test and at the DNA level. The DNA sequence of the alpha1 gene revealed a C-->G transversion at position 89, changing the local positively charged histidine to a neutral glutamine. This mutant has been previously described in a Yemenite woman and two apparently unrelated Somali males. Our case is the first showing Hb Buffalo in combination with Hb S and a G6PD deficiency, and is again observed in a Somali. No functional abnormalities associated with mutations at this amino acid residue are reported in the literature. Also, in this case no sign of any hematological abnormalities that could not be explained by the Hb S heterozygosity G6PD deficiency was found. The abnormal alpha chain is expressed at the expected rate and without thalassemic effect or instability. The mutated alpha chain seems to associate with a slight preference to the beta(A) (15%) rather than with the beta(S) counterpart. The sum of both Hb A(Buffalo) and Hb S(Buffalo) results in about 19-20% of total Hb. This figure is in agreement with a stable mutant of the alpha1 gene.
The Hemoglobinopathies and Red Cell Diagnostics, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Cornelis L
CL
Harteveld
Peter
P
Van Delft
Nicole
N
Akkermans
Sandra
S
Arkesteijn
Irene H
IH
Van Rooijen-Nijdam
Peter J M J
PJ
Kok
Florens G A
FG
Versteegh
Piero C
PC
Giordano
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D004912:Erythrocytes / Q000502:physiology; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006242:Haptoglobins / Q000032:analysis; D006451:Hemoglobin, Sickle / Q000031:analogs & derivatives* / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D017422:Sequence Analysis, DNA; D006442:Glycated Hemoglobin
D005954:Glucosephosphate Dehydrogenase; D006242:Haptoglobins; D006451:Hemoglobin, Sickle; D006455:Hemoglobins, Abnormal; C475068:hemoglobin Buffalo; C024241:glycated hemoglobin S; D006442:Glycated Hemoglobin