Clinico-mutational profile and the impact of splenectomy in children with glucose-6-phosphate isomerase deficiency

There is lack of literature regarding role of splenectomy in hemolytic anemias due to Glucose-6-phosphate isomerase (GPI). GPI deficiency is a rare RBC enzymopathy of glycolytic pathway. Most of them present with severe disease requiring frequent transfusions. In this study, we report the effect of splenectomy in the world's largest cohort of GPI deficiency patients. To describe the clinical, mutational and laboratory parameters of GPI deficiency patients and to compare their pre and post splenectomy transfusion requirement. Study Design – Ambispective study Sample Size – 18 Patients were screened for GPI deficiency in the congenital non-spherocytic hemolytic anemia (CNSHA) group. Detailed history including demographic, clinical data, transfusion details were noted. Hematological parameters and RBC enzyme activity was estimated using spectrophotometry. Genetic study was done by restriction fragment length polymorphism (RFLP) and confirmation by Sanger's sequencing. Patients were followed up after splenectomy. 77.7% (14/18) patients had significant hepatosplenomegaly. Median ferritin levels were 890 ng/ml with 7 patients on oral iron chelation. The nutritional status assessed as per IAP growth charts revealed significant growth retardation. All the patients had severe anemia with mean Hb of 6.4 g/dl and macrocytosis with mean MCV of 129.2fl. Laboratory features were suggestive of hemolysis with elevated levels of reticulocyte count, LDH and indirect bilirubin. The mean GPI enzyme activity was 28.75 IU/g Hb. Out of 18 patients in our cohort, 10 underwent splenectomy at the median age of 7 years. 5 out of 10 patients remain transfusion free post-splenectomy at median follow up of 54 months. There was statistically significant reduction (p<0.05) in transfusion requirement post-splenectomy. Mean hemoglobin levels increased from 6.2gm% to 8.1gm% post-splenectomy. Mean reticulocyte counts reduced from 7.4% to 4.8% post-splenectomy. 15 out of 18 GPI deficiency patients had the pathogenic c.1040G>A(p.Arg347His) homozygous mutation. We have emphasized on the overall benefit of splenectomy and the need for genetic counselling and antenatal diagnosis.