Pyruvate Kinase Deficiency: Current Challenges and Future Prospects.

Area of Science:

• Hematology
• Genetics
• Rare Diseases

Background:

• Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder causing chronic hemolytic anemia with variable severity and complications.
• Phenotypic heterogeneity is observed across age groups, impacting transfusion needs and complication rates.
• Diagnosis involves clinical suspicion, exclusion of other anemias, reduced pyruvate kinase (PK) activity, and PKLR gene mutation confirmation.

Purpose of the Study:

• To review current challenges in diagnosing and managing pyruvate kinase deficiency.
• To discuss emerging therapeutic strategies, including novel drugs and gene therapy.
• To highlight the importance of improving patients' quality of life.

Main Methods:

• Review of current literature on pyruvate kinase deficiency diagnosis and management.
• Analysis of diagnostic criteria, including enzyme activity assays and genetic testing.
• Evaluation of existing and novel therapeutic approaches, including supportive care, splenectomy, enzyme activators, and gene therapy.

Main Results:

• Diagnosis relies on a combination of clinical presentation, biochemical assays, and genetic confirmation.
• Supportive care and transfusions are standard, while splenectomy carries risks.
• Mitapivat has shown significant clinical benefit, and gene therapy is under investigation.

Conclusions:

• PKD diagnosis and management present ongoing challenges.
• Novel therapies like mitapivat and gene therapy hold promise for future treatment.
• Focusing on quality of life is crucial for patients with pyruvate kinase deficiency.