Role of Next-Generation Sequencing in Deciphering Congenital Hemolytic Anemia: A Case of Multiple Mutations Leading to Dual Congenital Hemolytic Anemia.

Before the widespread availability of next-generation sequencing (NGS), the diagnosis of hereditary spherocytosis (HS) and dehydrated hereditary stomatocytosis (DHS) was predominantly clinical. Here, we describe a patient with both HS and DHS who was initially treated for HS until NGS revealed that she had concomitant HS and DHS, leading to a pivot in clinical management. A 21-year-old female patient presented for evaluation of hemolytic anemia during pregnancy. The patient was clinically diagnosed with HS and treated with as-needed transfusions, with a plan for splenectomy. NGS revealed both HS and DHS. Thus, splenectomy was canceled, and aspirin was started. While treatments for HS and DHS differ greatly, in this case, where the patient has both, it is critical that treatment for DHS is prioritized because of the high risk of thromboembolic events following splenectomy. Early genetic evaluation is critical to provide an accurate diagnosis and to guide appropriate management.