Background: Most patients with anemia are diagnosed via clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed albeit going through an exhaustive workup. Genetic testing is complicated by the large number of genes involved with rare anemias and the similarities in the clinical presentation.
Objective: We aimed to enhance the diagnosis rates of patients with congenital anemias by using genetic targeted next generation sequencing.
Methods: Genetic diagnosis was performed by gene-capture followed by next generation sequencing of over 90 genes known to cause anemia syndromes.
Results: Genetic diagnosis was achieved in 15 out of 21 patients (71%). The average time from presentation to diagnosis was 12.2 years (STD 13.56). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis (DHS), 2 patients with elliptocytosis, 2 patients with sideroblastic anemia and one with CDA type IV. In 8 patients the genetic diagnosis was different than the pre-test presumed diagnosis.
Discussion: Targeted next generation sequencing lead to an accurate diagnosis of over 70% of patients with rare anemias. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients’ treatment and enable genetic counseling.
**This research was done as part of the pediatric residency requirements. Thanks to this study, sequencing is now performed clinically through the public health care system.
