Pyruvate kinase deficiency
- Josef T Prchal, MD
Josef T Prchal, MD
- Professor of Medicine
- University of Utah
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
Pyruvate kinase (PK) deficiency is the most common cause of congenital non-spherocytic chronic hemolytic anemia and is the result of an erythrocyte enzyme defect. It is an autosomal recessive condition caused by a deficiency of erythrocytic PK. Although the gene frequency for PK deficiency is far lower than that for glucose-6-phosphate dehydrogenase (G6PD) deficiency, the vast majority of patients inheriting G6PD deficiency never suffer acute or chronic hemolysis, whereas chronic hemolysis of variable severity is common in those with PK deficiency.
The molecular biology, clinical presentation, diagnosis, and treatment of PK deficiency are reviewed here [1,2]. An approach to the patient with suspected hemolytic anemia and an overview of the congenital hemolytic anemias in children are presented separately. (See "Diagnosis of hemolytic anemia in the adult" and "Overview of hemolytic anemias in children".)
Pyruvate kinase (PK) enzymes consist of several isoforms; they are products of two distinct M and PK LR genes both encoding an enzyme that catalyzes the transphosphorylation of phosphoenolpyruvate into pyruvate and ATP:
●The M (muscle) gene is expressed in muscle, brain, white blood cells, and platelets; it is located on chromosome 15q22. The M1 and M2 isoforms are the result of a differential processing of this single gene transcript. The M2 isoform is the dominant fetal form, and it is replaced after birth largely by the M1 isoform. The M2 isoform persists in adult life in white cells and platelets. In erythroid progenitors, it is progressively replaced by the R form.
●The L (liver) and R (red cell) isoenzymes are encoded by the LR gene on chromosome 1q21; these isoforms vary because of a differential use of tissue-specific promoters, as well as different exons at the 5' coding region. The R form, unique to erythrocytes, is 33 amino acids larger than the L form, which is unique to hepatocytes.
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- MOLECULAR BIOLOGY
- Mechanism for hemolysis
- Compensatory increase in oxygen delivery
- Disturbed iron metabolism
- CLINICAL AND LABORATORY FINDINGS
- Hemolytic anemia
- Possible protection from malaria
- Markers of hemolysis
- Reduced PK enzymatic activity
- When to test
- Diagnostic criteria
- Differential diagnosis
- Iron overload
- Folic acid
- Hematopoietic cell transplantation
- Gene transfer
- SUMMARY AND RECOMMENDATIONS