Hereditary Pyropoikilocytosis as a Modifier of Sickle Cell Disease Severity

Mutations that alter the structure of red blood cells, including the mutations that cause sickle cell disease (SCD), are common globally because they protect against malaria. Patients with SCD rarely develop severe anemia that requires blood transfusions before 6 months of age. We present the case of a patient with SCD who developed severe anemia requiring a blood transfusion at 6 weeks old and subsequent transfusions throughout her first two and a half years of life. Next-generation sequencing genetic testing revealed that the patient also had hereditary pyropoikilocytosis (HPP), a severe form of hereditary elliptocytosis (HE), and was heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Following splenectomy, the frequency of her transfusions slightly decreased. This case demonstrates that HPP modifies the severity of SCD and highlights the importance of considering additional hematologic conditions and obtaining genetic testing in patients with SCD and early-onset anemia.