The levels of zeta, gamma, and delta chains in patients with Hb H disease.
Details are given of a study of blood samples from 24 patients with Hb H disease from different Mediterranean countries and from the Far East. Four different types of alpha-thal-1 (--) were observed, namely -(alpha) (approximately 20.5-kb deletion); --MED-I (approximately 17.5-kb deletion); --MED-II (greater than 26.5-kb deletion); and --SEA (approximately 18-kb deletion, in Orientals only). The alpha-thal-2 was mainly of the deletion type (16 with the 3.7-kb deletion; 1 with the 4.2-kb deletion), while 4 of the 7 patients with a nondeletional type had the five-nucleotide deletion at the donor splice site of the first intron of the alpha 2 gene. All patients had a mild-to-moderate hemolytic anemia; no significant differences in hematology were observed between the groups. Hb A2 was decreased to about one-third of the normal level. The Hb H formation varied considerably and its quantitation was not always satisfactory. Patients with Hb H disease due to any alpha-thal-1 combined with a nondeletional alpha-thal-2 had the highest Hb H levels and a more marked anemia. The zeta chain production was small and absent in patients with the MED-II type of alpha-thal-1 because this deletion included the zeta and psi zeta genes. The highest zeta chain levels were present in the four patients with the SEA type of alpha-thal-1. The gamma chain production was increased, particularly in patients with a mutation of C----T at position -158 to the G gamma globin gene. This gamma chain was primarily present as Hb Bart's (or gamma 4) and only about 15% was recovered as Hb F or alpha 2 gamma 2. The evaluation of the rate of gamma chains produced in these patients was greatly facilitated by data from one patient who had Hb H disease and a heterozygosity for the A gamma-beta+-HPFH. The low levels of Hb A2 and of Hb F (relative to Hb Bart's) can be explained by a decreased affinity of alpha chains for delta and gamma chains as compared with beta chains in conditions of severe alpha chain deficiency.
Kutlar
F
F
Department of Cell and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Gonzalez-Redondo
J M
JM
Kutlar
A
A
Gurgey
A
A
Altay
C
C
Efremov
G D
GD
Kleman
K
K
Huisman
T H
TH
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis; D005260:Female; D006447:Hemoglobin H / Q000032:analysis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D012150:Polymorphism, Restriction Fragment Length; D013789:Thalassemia / Q000097:blood* / Q000235:genetics
D006455:Hemoglobins, Abnormal; D010446:Peptide Fragments; D004247:DNA; D006447:Hemoglobin H