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

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Erythrocyte lifespan is normally 120 days; hemolytic anemia shortens this.
• Intrinsic causes include pyrimidine 5'-nucleotidase (P5N) deficiency, often causing nonspherocytic hemolytic anemia.
• P5N deficiency results from mutations in the NT5C3A gene.

Observation:

• A 65-year-old female with systemic lupus erythematosus and splenectomy presented with recurrent hemolytic crises.
• Peripheral blood smear showed macrocytic anemia and basophilic stippling.
• Osmotic fragility tests and G6PD levels were normal.

Findings:

• Next-generation sequencing identified a homozygous c.693+1G>A variant in the NT5C3A gene.
• This variant is classified as possibly pathogenic and linked to P5N deficiency.
• The genetic findings correlated with the patient's non-immune hemolytic anemia presentation.

Implications:

• Next-generation sequencing is crucial for diagnosing rare hemolytic anemias.
• Genetic counseling and continued follow-up are essential for patients with enzyme deficiencies.
• Molecular diagnostics improve understanding and management of inherited hemolytic anemias.