부산대학교 도서관

Glucose-6-phosphate isomerase (GPI, EC 5.3.1.9) is a dimeric enzyme that catalyses the reversible isomerisation of glucose-6-phosphate (G6P) to fructose-6-phosphate (F6P), the second reaction step of glycolysis. GPI deficiency is the second most common erythro-enzymopathy of anaerobic glycolysis, after pyruvate kinase. The gene locus encoding GPI is located on chromosome 19q13.1 and contains 18 exons. So far about 50 cases of GPI deficiency have been described, and 29 mutations have been reported at the nucleotide level: 25 missense, 2 nonsense and 2 splice site. The aim of this study is to describe the hematological, biochemical and molecular characteristics of two new families affected by GPI deficiency with chronic hemolytic anemia. Case1: The propositus was a 1 yrs old boy of Northern Italian origin with chronic hemolytic anemia and need for blood transfusion in concomitance of infectious episodes. At the time of the study Hb was 7.6 g/dL, reticulocytes 231x109/L, total bilirubin 1.4 mg/dL. The study of the most important red cell enzymes revealed a very low GPI activity (12.5% of normal). The parents were not consanguineous, and displayed intermediate GPI activity (66% of normal in both). The sequence of complete erythrocyte GPI gene revealed the presence of two new missense mutations: G145C (Gly49Arg) and C921A (Phe307Leu). Since both these aminoacids are conserved in eukaryotic GPI enzymes, the mutations G145C and C921A are likely to impair the enzyme function or stability. Case2:The propositus was a 8 yrs. old girl of Southern Italian origin with a history of chronic hemolytic anemia and occasional need for blood transfusion. At the age of 7 yrs. she was splenectomised reducing the need for blood transfusion. At the time of the study Hb was 9.4 g/dL, reticulocytes 364x109/L, total bilirubin 12.3 mg/dL. The propositus was homozygote for Gilbert’s syndrome. GPI activity was 20% of normal. The parents were not consanguineous, and displayed intermediate GPI activity (55% and 61% of normal). The sequence of complete erythrocyte GPI gene revealed the presence of two missense mutations, G301A (already described in an Italian patient by Baronciani et al Blood 88:2306,1996) and the new variant G1009A, which result in the aminoacidic substitutions Val101Met and Ala337Thr respectively.