pyruvate kinase deficiency of red cells

Pyruvate kinase deficiency of red cells is a genetic metabolic disorder that primarily affects red blood cells, leading to chronic nonspherocytic hemolytic anemia. The condition arises from pathogenic variants in the PKLR gene, which impair the production of ATP in red cells and result in their premature destruction. It typically presents early in life, although the severity can range from compensated hemolysis without apparent anemia to severe, life‐threatening anemia. The disorder is uncommon, affecting roughly 1 to 9 in every 100,000 individuals.

The clinical presentation of pyruvate kinase deficiency of red cells is primarily marked by hematologic abnormalities. Characteristic findings include erythroid hyperplasia, reduced red cell pyruvate kinase levels, reduced haptoglobin, reticulocytosis, and chronic hemolytic anemia, with associated features such as jaundice, pallor, hepatomegaly, and splenomegaly occurring in all affected individuals. In some cases, a subset of patients may also experience nonimmune hydrops fetalis and intrauterine growth retardation. Not all individuals experience all features, and severity varies considerably.

Pyruvate kinase deficiency of red cells is caused by pathogenic variants in the PKLR gene. This gene encodes an enzyme that plays a key role in the glycolytic pathway, and its deficiency leads to inadequate ATP production in red blood cells, making them more prone to hemolysis. The condition is inherited in an autosomal recessive pattern, which means that an individual must inherit two copies of the mutated gene—one from each parent—to exhibit symptoms. Families may benefit from genetic counseling to better understand the inheritance risks and implications for other family members.

Currently, management of pyruvate kinase deficiency of red cells focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Treatment is individually tailored and typically involves a multidisciplinary team to address the hematologic issues and any complications that arise. Regular surveillance is an essential part of long-term care, as ongoing monitoring can help identify potential complications at an early stage. Genetic counseling is also recommended to help patients and their families understand the implications of the autosomal recessive inheritance pattern and explore available supportive services.

The long-term outlook for individuals with pyruvate kinase deficiency of red cells is highly variable. With current standards of care and regular surveillance, many individuals manage their symptoms well into adulthood, although the course of the disorder can range from mild, compensated hemolysis to more severe anemia requiring ongoing medical intervention. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists and genetic counselors to discuss management strategies and ensure that treatment is adapted to the individual’s needs.

Several clinical trials are currently underway exploring new treatment approaches for pyruvate kinase deficiency of red cells. Individuals interested in learning more about these investigational therapies are encouraged to consult ClinicalTrials.gov or speak with their healthcare team about potential eligibility for ongoing studies.