Unusual cause of hemolytic anaemia: Glucose phosphate isomerase deficiency

Glucose phosphate isomerase (GPI) deficiency is a rare autosomal recessive disorder that causes hereditary nonspherocytic hemolytic anaemia (HNSHA). It is caused by homozygous or compound heterozygous mutation of the GPI gene on chromosome 19q13. Approximately 57 GPI mutations have been reported at the molecular level. A 4-year-old and 6-month-old boy presented with progressive pallor along with multiple blood transfusion requirements since four months of age. He had severe hemolytic anaemia associated with macrocytosis, reticulocytosis, neutropenia, and hyperbilirubinemia. Whole-exome sequencing showed that he carried a specific variant in the glucose phosphate isomerase gene, denoted as c.1040G>A p.Arg347His, which is a Homozygous Autosomal recessive inherited Pathogenic mutation found in Exon 12. This report highlights the clinical features and molecular etiology of an Indian patient with GPI deficiency, a rare cause of hereditary hemolytic anaemia. Through whole-exome sequencing, a specific variant in the glucose phosphate isomerase gene was identified, which is linked to Non-spherocytic Hemolytic anaemia. Patients with GPI deficiency require medical management during childhood to monitor for potential complications and prevent hemolytic crises. With proper management, patients with GPI deficiency can lead a relatively everyday life with normal expectations of growth and development.