Transient infantile HPP. An African American girl presented within the first day of life after delivery at term with nonimmune hemolytic anemia and neonatal jaundice. She was treated with triple phototherapy but did not require RBC transfusion. (A) The blood smear of the patient with HPP showing marked anisocytosis and poikilocytosis with bizarre microcytes and fragmented cells along with elliptocytes (scale bar = 14 µm). (B) The blood smear of the mother, who had a normal Hgb and reticulocyte count, was notable for elliptocytes indicating HE. (C) Ektacytometry showed the trapezoid curve characteristic for HE and HPP with decreased deformability for both mother and patient. The patient's sample was sequenced by NGS on an RBC membrane gene panel, which revealed the SPTA1 HE-causing variant c.460_463insTTG (p.L155dup) as well as the SPTA1 c.6531-12C>T polymorphism known as α^LELY. Targeted sequencing for these variants revealed that the mother was heterozygous for SPTA1 p.L155dup. The mother did not carry α^LELY, which was presumably inherited by the father. The compound heterozygosity of an HE-causing SPTA1 mutation in trans to α^LELY confirmed the diagnosis of infantile HPP. The child continued to have a mild anemia with reticulocytosis (Hgb, 10.2 g/dL with 3.8% reticulocytes) and poikilocytosis, with RDW up to 18.7% at her 2-year-old follow-up, but a CBC with reticulocyte count and blood smear at 5 years of age indicated transition to a nonhemolytic HE phenotype. RDW, RBC distribution width.