Details

Autor(en) / Beteiligte

• Luke, Neeti
• Hillier, Kirsty
• Al-Samkari, Hanny
• Grace, Rachael F.

Titel

Updates and advances in pyruvate kinase deficiency

Ist Teil von

• Trends in molecular medicine, 2023-05, Vol.29 (5), p.406-418

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Pyruvate kinase (PK) deficiency is a genetically and clinically heterogeneous congenital hemolytic anemia which manifests with a wide range of symptoms and complications.Given the clinical heterogeneity, clinicians should have a high suspicion of PK deficiency in patients with congenital hemolytic anemias, and both red cell enzyme and genetic testing should be pursued.Complications in PK deficiency can be associated with significant morbidity and mortality in transfused and non-transfused patients, including iron overload, osteopenia, and impact on quality of life and mental health, which require regular monitoring and management.A definitive diagnosis of PK deficiency has become critical with the availability of disease-modifying therapy with mitapivat, an oral PK activator which increases hemoglobin and decreases hemolysis in many patients, as well as the potential future curative option of gene therapy. Mutations in the PKLR gene lead to pyruvate kinase (PK) deficiency, causing chronic hemolytic anemia secondary to reduced red cell energy, which is crucial for maintenance of the red cell membrane and function. Heterogeneous clinical manifestations can result in significant morbidity and reduced health-related quality of life. Treatment options have historically been limited to supportive care, including red cell transfusions and splenectomy. Current disease-modifying treatment considerations include an oral allosteric PK activator, mitapivat, which was recently approved for adults with PK deficiency, and gene therapy, which is currently undergoing clinical trials. Studies evaluating the role of PK activators in other congenital hemolytic anemias are ongoing. The long-term effect of treatment with disease-modifying therapy in PK deficiency will require continued evaluation.