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

Abstract

Red blood cell enzyme deficiencies are a rare category of hemolytic anaemia presented in children with varying degrees of hemolysis, indirect hyperbilirubinemia and splenomegaly. Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme deficiency, followed by pyruvate kinase deficiency. 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 clinical symptoms, diagnostic strategy, management and incidence of enzyme deficiencies in Indian patients. Most RBC enzyme deficiencies are inherited in an autosomal recessive fashion except for glucose 6- phosphate dehydrogenase, 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 are important to guide antenatal diagnosis in subsequent pregnancies. Management of RBC enzymopathies will depend 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 like Mitapivat have proven to be beneficial in adults with PK deficiency and ongoing trials in children are showing promising results.