A family affair—Severe fetal and neonatal hemolytic anemia due to novel alpha‐spectrin mutations in two siblings. Issue 3 (19th December 2019)

• Record Type: Journal Article
• Authors: Donepudi, Roopali; Westerfield, Lauren; Stonecipher, Ashley; A. Nassr, Ahmed; Cortes, Magdalena S.; Espinoza, Jimmy; Belfort, Michael; Shamshirsaz, Alireza
• Is Part Of: American journal of medical genetics. Volume 182:Issue 3(2020)
• Page Start: 561
• Page End: 564
• Publication Date: 2019-12-19
• Subjects: fetal anemia -- fetal surgery -- hereditary spherocytosis; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61455
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: Hereditary spherocytosis (HS) is the most common cause of inherited, nonimmune hemolytic anemia. When inherited in an autosomal dominant fashion, the anemia is typically mild. However, severe, transfusion‐dependent anemia is seen in autosomal recessive HS, which is often associated with deficient or absent red blood cell membrane protein alpha‐spectrin. We report a 26‐year‐old para one who was referred to our center at 28 weeks' gestation due to concerns for fetal anemia. Evaluation revealed elevated peak systolic velocity in the middle cerebral artery by Doppler scan and fetal cardiomegaly. Fetal hematocrit obtained by sampling the umbilical vein was 9% confirming severe fetal anemia. Fetal peripheral smear was consistent with hereditary spherocytosis. Genetic analysis of both parents confirmed heterozygosity for the SPTA1 variants (pathogenic variant c.4180del (p.C1394Afs*25), and a variant of uncertain significance, c.1677G>T (p.G449G)) detected by a hemolytic anemia panel in the patient's first child. It is important to consider genetic causes of anemia in patients presenting with severe nonimmune fetal anemia, including autosomal recessive HS. We present a case of autosomal recessive HS with a novel pathogenic variant in the SPTA1 gene which resulted in significant impact on prenatal management.