Erythrocyte pyruvate kinase deficiency: 2015 status report

Abstract

Over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia associated with red cell pyruvate kinase deficiency (PKD) has expanded. Nonetheless, there remain significant gaps in our knowledge with regard to clinical care and monitoring. Treatment remains supportive with phototherapy and/or exchange transfusion in the newborn period, regular or intermittent red cell transfusions in children and adults, and splenectomy to decrease transfusion requirements and/or anemia related symptoms. In this article, we review the clinical diversity of PKD, the current standard of treatment and for supportive care, the complications observed, and future treatment directions.Am. J. Hematol. 90:825–830, 2015. © 2015 Wiley Periodicals, Inc.

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

“…Treatment is generally supportive with common interventions including splenectomy and blood transfusions. 5,6 Thus, there is an unmet medical need for novel therapies that address the underlying basis for PK deficiency.…”

“…11 PK deficiency is an autosomal recessive disease, and patients are either homozygous, or more commonly, compound heterozygous for 2 mutant PK-R (mtPK-R) alleles. 12 A variety of experimental therapies, including gene therapy, [13][14][15] have been proposed for PK deficiency 5,16,17 ; however, there are no approved drugs that directly target mutated PK-R.…”

Worldwide study of hematopoietic allogeneic stem cell transplantation in pyruvate kinase deficiency

“…2 The treatment for PKD is mainly supportive, and consists of regular red blood cell transfusions, splenectomy and chelation therapy for iron overload. 3 Hematopoietic allogeneic stem cell transplantation (HSCT) has the potential to cure PKD. However, there is little experience of applying HSCT in PKD.…”

Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency

“…4,42 Anemia may be surprisingly well tolerated in PK-deficient patients 43 probably because of the increased red cell 2, 3-DPG content, which is responsible for a rightward shift in the oxygen dissociation curve of hemoglobin. Early onset of anemia is usually associated with a more severe clinical course.…”

“…Early onset of anemia is usually associated with a more severe clinical course. 4,42,44,45 Notably, since splenectomy is not indicated in some other forms of chronic hemolytic anemia, such as hereditary stomatocytosis, 46 the diagnosis of PK deficiency should be established and comorbidity of stomatocytosis or other thrombophilic disorders should be excluded before splenectomy is performed. The anemia tends to improve with age, and is relatively constant in adulthood, although exacerbations requiring occasional transfusion may occur because of the stress of acute infections or pregnancy.…”