568 - A Novel Method for Hereditary Hemolytic Anemia- Case Series and Literature Review

Poster Number: 568
Publication Number: 568.321

WENDY DE LA RUA, The Children's Regional Hospital at Cooper, CHERRY HILL, NJ, United States; Christian M. Bruni, The Children's Regional Hospital at Cooper, Camden, NJ, United States; Rafat Ahmed, Cooper Medical School of Rowan University, Camden, NJ, United States; Maria Irene Scarano, Cooper Medical School of Rowan University, Camden, NJ, United States; Michael Hardiman, The Children's Regional Hospital at Cooper, mount laurel, NJ, United States

Background: Hemolytic anemia is the premature destruction of red blood cells due to erythrocytes’ membrane or enzymatic defect, or globin gene variation.  These anomalies can be inherited or acquired. Diverse diagnostic evaluations have been used throughout the years. However, as science is evolving there have been less invasive and more informative tests available that can diagnose complex and unclear presentations. Next gene sequencing has simplified our practice to evaluate and diagnose these patients.

Objective: This case series aims to describe four interesting cases with hemolytic anemia that required Next gene sequencing for diagnosis

Design/Methods: Use of Next gene sequencing for diagnosis of refractory hemolytic anemia

Results:
First case is a 16-month-old infant with refractory anemia in whom, comprehensive hemolytic work-up was done and next gene sequencing revealed two heterozygous missense alterations in the alpha spectrin gene (SPTA1), as well as a common phenotype modifying polymorphism alpha-LELY and diagnosed with Hereditary Pyropoikilocytosis.Second case is a full-term newborn found to have severe normocytic anemia and Coombs positive requiring NICU admission for management and comprehensive hematology workup. Next gene sequencing revealed that he was heterozygous for a pathogenic variant of ANK1 and diagnosed with autosomal dominant Hereditary Spherocytosis.Third case is a 17-year-old adopted male with unknown biological family history that presented with severe symptomatic hemolytic anemia and splenomegaly that was refractory to treatments. Next gene sequencing was obtained and showed a common SPTA1 gene variant in alpha-LELY polymorphism and a segmental variation in beta spectrin gene which is seen in Hereditary Spherocytosis.Fourth case is a 10-year-old female from Jamaica that presented with splenomegaly and symptomatic hemolytic anemia. Next gene sequencing to assess the cause of her hemolytic anemia, revealed a pathologic variant of Spectrin Alexandria in the alpha spectrin gene (SPTA-1) supportive of red blood cell membrane disorder often seen with Hereditary elliptocytosis/ pyropoikilocytosis.
Conclusion(s): All these patients had similar but complex medical presentations; however, on gene analysis three were noted to have missense mutations of the SPTA1 gene, while one was found to have pathogenic alterations of ANK1. Patients presenting with refractory hemolytic anemia, those requiring several transfusions, or those in need of splenectomy might benefit from next gene sequencing as a diagnostic test for more specific and definitive management.