Molecular analysis of glucose phosphate isomerase deficiency associated
with hereditary hemolytic anemia
H Kanno, H Fujii, A Hirono, Y Ishida, S Ohga, Y Fukumoto, K Matsuzawa, S Ogawa and S Miwa
Okinaka Memorial Institute For Medical Research, Tokyo, Japan.
We report here two new cases of glucose phosphate isomerase (GPI)
deficiency associated with hemolytic anemia and present the results of
molecular analysis of the five Japanese GPI variants. A Japanese girl (GPI
Fukuoka) had an episode of prolonged neonatal jaundice and at 3 years of
age was admitted due to acute hemolytic crisis occurring with upper
respiratory tract infection. Red blood cell (RBC) GPI activity was
decreased to 11.8% of normal and the reduced glutathione (GSH) level of
RBCs was slightly decreased. A 54-year-old Japanese man (GPI Iwate) was
hospitalized due to chronic active hepatitis, and compensated hemolysis was
noted. RBC GPI activity of the proband was decreased to 18.8%, and the GSH
content was about half of the normal mean value. Sequencing of the
reticulocyte GPIcDNA showed homozygous missense mutations 1028CAG-->CGG
(343Gln-->Arg), 14ACC-->A7C (5Thr-- >lle), 671ACG-->A7G
(224Thr-->Met), and 1615GAC-->AAC (539Asp-->Asn) in GPI Narita,
GPI Matsumoto, GPI Iwate, and GPI Fukuoka, respectively. We also identified
GPI Kinki as a compound heterozygote of 1124ACA-- >AGA(375Thr-->Arg)/
1615GAC-->AAC(539Asp-->Asn). Our findings, together with the previous
results of other investigators, showed that the GPI gene mutations so far
identified were heterogeneous, although most GPI variants had common
biochemical characteristics such as heat instability and normal kinetics.
Several amino acid substitutions were identified in the proximity of the
catalytically important amino acid residues such as Ser/Asp 159/160,
Asp341, and Lys518, which have been identified in the structural analysis
of the pig GPI. The molecular characterization of human GPI variants,
therefore, may provide new insights into the genotype-phenotype correlation
of GPI deficiency as well as the structure-function relationship of this
enzyme.
Volume 88,
Issue 6,
pp. 2321-2325,
09/15/1996
Copyright © 1996 by The American Society of Hematology
