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

Abstract

Background

There is a lack of literature on the role of splenectomy in hemolytic anemias due to glucose-6-phosphate isomerase (GPI) deficiency. GPI deficiency is a rare red blood cell (RBC) enzymopathy of the glycolytic pathway. Most 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. The study aimed to describe the clinical, mutational, and laboratory parameters of patients with GPI deficiency. A comparison of the transfusion requirement pre- and post-splenectomy is also included.

Material and methods

The ambispective study was performed from 2017 to 2023. Patients with congenital non-spherocytic hemolytic anemia (CNSHA) were screened for GPI deficiency. Detailed history, including demographic, clinical data, and transfusion details, were noted. Hematological parameters and RBC enzyme activity were estimated using spectrophotometry. The genetic study was done using restriction fragment length polymorphism, and confirmation was obtained through Sanger's sequencing. Patients were followed up after splenectomy.

Results

Eighteen patients were diagnosed with GPI deficiency. About 3/4th (14/18; 77.7 %) had significant hepatosplenomegaly. Median serum ferritin levels were 890 ng/ml. Seven patients were on oral iron chelation. The nutritional status assessed as per the Indian Academy of Pediatrics growth charts revealed significant growth retardation. All the patients had severe anemia (mean Hb: 6.4 g/dl) and macrocytosis (mean MCV: 129.2 fl). Laboratory features of hemolysis were evident with reticulocytosis, raised serum lactate dehydrogenase, and indirect bilirubin. The mean GPI enzyme activity was 28.75 IU/g Hb.

Ten (55.5 %) patients underwent splenectomy at a median age of 7 years. Five remain transfusion-free post-splenectomy at a median follow-up of 54 months. Other 5 had a significant reduction in transfusion requirement post-splenectomy (p < 0.05). Post-splenectomy, the mean hemoglobin levels increased from 6.2 to 8.1 gm%, and the mean reticulocyte counts reduced from 7.4 % to 4.8 %. Fifteen of 18 had the pathogenic c.1040G > A(p.Arg347His) homozygous mutation.

Conclusion

The study demonstrates the benefit of splenectomy in patients with GPI deficiency.