Glycolytic pathway defects are autosomal recessive red blood cell metabolic disorders that cause nonspherocytic hemolytic anemia.
The glycolytic pathway is one of the body's important metabolic pathways. It involves a sequence of enzymatic reactions that break down glucose (glycolysis) into pyruvate, creating the energy sources adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). Various inherited defects in enzymes of the pathway may occur (1).
The most common defect is:
Pyruvate kinase deficiency
Other defects that cause hemolytic anemia include deficiencies of:
Hexokinase
Glucose phosphate isomerase
Phosphofructokinase
In all of these pathway defects, hemolytic anemia occurs only in patients who are homozygous for the mutation. The exact mechanism of hemolysis is unknown.
Symptoms are related to the degree of anemia and may include jaundice and splenomegaly. Blood smear findings are nonspecific, such as echinocytes (burr cells) and anisopoikilocytosis but red blood cell morphology may appear overall normal.
Biochemical testing of red blood cell (RBC) enzyme activity (eg, pyruvate kinase activity) is diagnostic but may be limited by recent transfusions and sometimes masking by reticulocytosis or assay interference from white blood cells. Genetic testing can also be performed.
Довідковий матеріал загального характеру
1. Luzzatto L. Diagnosis and clinical management of enzymopathies. Hematology Am Soc Hematol Educ Program. 2021;2021(1):341-352. doi:10.1182/hematology.2021000266
Treatment of Glycolytic Pathway Defects
Folic acid during hemolysis
Transfusions if needed
Sometimes splenectomy
Patients may require folic acid 1 mg orally once a day or transfusions. Iron chelation may be needed if there is evidence of iron overload.
For pyruvate kinase deficiency, mitapivat, an oral activator of RBC pyruvate kinase, may be considered for adults with symptomatic anemia or transfusion dependence (1).
In severe cases, patients may be transfusion dependent, in which case, splenectomy may be done. Hemolysis and anemia persist after splenectomy, although some improvement may occur, particularly in patients with pyruvate kinase deficiency.
Довідковий матеріал щодо лікування
1. Al-Samkari H, Galacteros F, Glenthoj A, et al. Mitapivat versus Placebo for Pyruvate Kinase Deficiency. N Engl J Med. 2022;386(15):1432-1442. doi:10.1056/NEJMoa2116634
