Hereditary Pyropoikilocytosis—a Frequently Fatal Prenatal Blood Disorder

A 17-year-old female patient was referred to us with a still undiagnosed hematological disorder characterized by hemolysis and hyperbilirubinemia. Prenatally, she had already received seven intrauterine transfusions for severe anemia (hemoglobin 3 g/dL) with fetal hydrops. She was delivered by Cesarean section at 36 weeks’ gestation. Postnatally, the anemia persisted with a hemoglobin level of 9.5 g/dL. Since then, she had undergone chronic transfusion treatment (target hemoglobin 8–9 g/dL) with more than 230 transfusions. In addition, she had received iron chelation therapy and undergone splenectomy and cholecystectomy. Her mother had a history of hemolytic crises (status post splenectomy; elliptocytes in blood smear) and her brother of moderate hemolysis. Thus, she was initially diagnosed with hereditary elliptocytosis (autosomal dominant inheritance). However, this condition could not sufficiently explain the severity of anemia. Genetic testing revealed a pathogenic homozygous variant in the SPTA1 gene (c.6 788 + 1 G > A, p.?), confirming the diagnosis of hereditary pyropoikilocytosis. This rare severe type of congenital hemolytic anemia is also characterized by elliptocytes in the blood smear (Figure) and affected individuals usually do not survive without intrauterine transfusion. The possibility of allogeneic stem cell transplantation as a curative treatment was discussed at times, but, with decreasing transfusion frequency, this option ultimately proved unnecessary.

Figure

Wright-Giemsa stain of the peripheral blood smear of the patient

Acknowledgement: We would like to thank Mr. Christian Welz from the Laboratory for Special Hematology/Oncology at the University Hospital Münster (UKM) for providing the images.

Dr. med. Daniel Ebrahimi-Fakhari, Prof. Dr. med. Claudia Rössig, Prof. Dr. med. Andreas H. Groll, Pädiatrische Hämatologie und Onkologie, Universitätsklinikum Münster, [e-mail]

Conflict of interest: The authors declare no conflict of interest.

Translated from the original German by Ralf Thoene, MD.

Cite this as: Ebrahimi-Fakhari D, Rössig C, Groll AH: Hereditary pyropoikilocytosis—a frequently fatal prenatal blood disorder. Dtsch Arztebl Int 2025; 122: 297. DOI: 10.3238/arztebl.m2025.0062