Severe Hereditary Pyropoikilocytosis/Hereditary Elliptocytosis-Like Phenotype Associated With a Heterozygous

Background: Hereditary elliptocytosis (HE) is typically a mild or asymptomatic red blood cell membrane disorder characterized predominantly by elliptocytes, whereas hereditary pyropoikilocytosis (HPP) represents the severe end of the HE spectrum, with early-onset hemolysis, marked poikilocytosis, red cell fragmentation, and pronounced membrane instability. We report a Cambodian girl with a severe HPP/HE-like phenotype associated with a heterozygous Case Presentation: A 7-year-old Cambodian girl born to nonconsanguineous parents was referred for evaluation of chronic transfusion-dependent hemolytic anemia that began in the neonatal period. She developed severe jaundice at 1 week of age, requiring intensive phototherapy, and required regular packed red blood cell transfusions from 2 weeks of age. Corticosteroid therapy was initiated when immune-mediated hemolysis was suspected, modestly prolonging the transfusion interval before being discontinued because of Cushingoid features. Physical examination revealed pallor, scleral icterus, and mild splenomegaly. Laboratory evaluation showed severe anemia, markedly elevated red cell distribution width, an inappropriately low reticulocyte count for the degree of anemia, a negative direct antiglobulin test, normal G6PD activity, and red cell morphological abnormalities, including poikilocytes, elliptocytes, and red cell fragments. Phenotype-guided clinical whole-exome sequencing identified a heterozygous Conclusion: This case illustrates the diagnostic complexity of severe HPP/HE-spectrum disease associated with a heterozygous