Hemolytic anemia due to red cell pyruvate kinase deficiency D52.2

Most common autosomal recessive enzyme defect of glycolysis.

Prevalence: 1-9 / 100 000

Infancy, newborn period

Clinically, patients with PK deficiency suffer from varying degrees of chronic hemolysis, ranging from:

• severe neonatal jaundice and fatal anemia at birth
• severe transfusion-dependent chronic haemolysis
• moderate hemolysis with exacerbation during infections
• to fully compensated hemolysis without obvious anemia.

Symptoms typically appear at birth. However, they may not be recognized until later because of the variable severity. Furthermore, chronic icterus, gallstones, iron overload and splenomegaly are common findings.

The diagnosis can be made on the basis of clinical features and laboratory results:

• variable degree of anemia
• reticulocytosis
• increased non-conjugated bilirubin level
• decreased haptoglobin level.
• Blood smear: acanthocytes (shrunken erythrocytes with spicules "datura" shape of erythrocytes.
• PK deficiency can be diagnosed by measuring the enzymatic activity of PK.
• Confirmation of the diagnosis requires genetic testing.

Note: Due to the fact that enzymatic activity depends on the age of red blood cells, PK deficiency can be masked by reticulocytosis.

The prognosis depends on the severity of the anemia. As with other chronic hemolytic diseases, gallstones and iron overload may develop, requiring adapted treatment.

1. Grace RF et al (2015) Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol 90:825-830.
2. Grace RF et al (2019) Safety and efficacy of mitapivat in pyruvate kinase deficiency. N Engl J Med 381:933-944.
3. Grace RF et al (2019) How we manage patients with pyruvate kinase deficiency. Br J Haematol 184:721-734.