Rare red cell enzymopathies in the Indian population: A comprehensive review

Abstract

Red blood cell enzyme deficiencies are a rare category of hemolytic anaemia that typically present in children with varying degrees of hemolysis, indirect hyperbilirubinemia and splenomegaly. Glucose 6-phosphate dehydrogenase (G6PD) is the most common enzyme deficiency, followed by pyruvate kinase deficiency (PKD). This article aims to understand the pathophysiology of the rare enzymopathies due to deficiencies in the Embden-Meyerhoff pathway, glutathione metabolism, hexose monophosphate shunt and nucleotide metabolism pathway, and to study the incidence, clinical symptoms, diagnostic strategy, and management of enzyme deficiencies in the Indian patients. Most red blood cell (RBC) enzyme deficiencies are inherited in an autosomal recessive fashion except for G6PD, and phosphoglycerate kinase deficiency which has X-linked inheritance. Presentation depends on the representation of the enzyme on different tissues of the body, hence some enzyme deficiencies may present with neurological or muscular manifestations. In patients with suspected hemolytic anaemia, complete blood count and peripheral smear help in differentiating from hemoglobinopathies, etc. To clinch the diagnosis enzyme levels and genetic testing may be required. These tests guide antenatal diagnosis in subsequent pregnancies. Management of RBC enzymopathies depends on the predominant symptoms and severity of hemolysis. Patients with marked hemolysis require regular blood transfusions and hence appropriate chelation therapy. Hematopoeitic stem cell transplant is attempted in patients with severe spectrum with variable results. Newer drugs, including mitapivat have proven to be beneficial in adults with PKD and ongoing trials in children are showing promising results.