Pyrimidine-5'-Nucleotidase Deficiency: a New Homozygous NT5C3A Mutation (c.693+1G>A variant)

Erythrocytes have an average lifespan of 120 days, after which they are typically removed by macrophages in the reticuloendothelial system. Hemolytic anemia can shorten erythrocyte lifespan, leading to varying clinical presentations depending on whether hemolysis occurs intravascularly or extravascularly. Among intrinsic causes of hemolysis, pyrimidine 5'-nucleotidase (P5N) deficiency is a notable condition, often presenting as nonspherocytic hemolytic anemia.

We report a case of a 65-year-old female patient with systemic lupus erythematosus and a history of splenectomy, who was admitted for evaluation of persistent hemolytic crises. Clinical examination, peripheral blood smear analysis, and genetic testing were performed, including next-generation sequencing to identify mutations in the NT5C3A gene associated with P5N deficiency.

The patient exhibited macrocytic anemia and basophilic stippling on peripheral blood smear, with normal results from osmotic fragility tests and G6PD levels. Genetic testing revealed a homozygous c.693+1G>A variant in the NT5C3A gene, classified as possibly pathogenic based on ACMG criteria. This variant is linked to P5N deficiency, which aligns with the patient's clinical presentation of non-immune hemolytic anemia.

The identification of the NT5C3A gene mutation through next-generation sequencing highlights the significance of molecular technologies in diagnosing rare forms of hemolytic anemia. This case underscores the necessity for genetic counseling for affected individuals and their families, as well as the importance of continued follow-up and supportive care in managing hemolytic anemia related to enzyme deficiencies.