Hemolytic anemia due to glucophosphate isomerase deficiency

Hemolytic anemia due to glucosephosphate isomerase (GPI) deficiency, also known as glucose-6-phosphate isomerase deficiency or phosphoglucose isomerase (PGI) deficiency, is a rare inherited metabolic disorder affecting red blood cells. GPI is an enzyme in the glycolytic (Embden-Meyerhof) pathway, which is the primary energy-producing pathway in red blood cells. When this enzyme is deficient, red blood cells cannot generate adequate energy (ATP), leading to their premature destruction (hemolysis). GPI deficiency is considered the second most common cause of hereditary nonspherocytic hemolytic anemia among glycolytic enzyme defects, after pyruvate kinase deficiency. Clinical features typically present in the neonatal or infantile period and include chronic hemolytic anemia of variable severity, jaundice (including neonatal hyperbilirubinemia that may require exchange transfusion), splenomegaly, and reticulocytosis. Some patients may experience hemolytic crises triggered by infections or other stressors. In severe cases, hydrops fetalis has been reported. A subset of patients may also exhibit mild neuromuscular manifestations, as GPI also functions as a neurotrophic factor (neuroleukin) outside of red blood cells, though neurological involvement is not a consistent feature. Treatment is primarily supportive. Red blood cell transfusions may be required during severe anemia or hemolytic crises, and folic acid supplementation is commonly recommended to support increased red cell production. Splenectomy has been performed in some patients with severe disease and may reduce transfusion requirements and improve hemoglobin levels, though hemolysis is not completely eliminated. Iron overload from chronic hemolysis and/or transfusions may necessitate iron chelation therapy. There is currently no curative treatment, though management of complications can significantly improve quality of life.

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