Introduction: Hemolytic disease of the fetus and newborn (HDFN) is a potentially life-threatening condition caused by maternal alloimmunization against fetal red blood cell (RBC) antigens. While most cases involve well-characterized antibodies such as anti-D, anti-c, or anti-K, antibodies against low-prevalence antigens (LPAs) — particularly those within the MNS blood group system — remain underrecognized and underreported. Case Presentation: We report a case of maternal alloimmunization against the paternally inherited low-prevalence antigen MUT (MNS35), carried on a hybrid glycophorin (GYPA*19, GP.Hut), across three pregnancies. The first pregnancy ended in fetal demise due to severe anemia at 33 weeks of gestation (WG). In a subsequent twin pregnancy, both neonates presented with severe HDFN after emergency cesarean section at 31 WG. Anti-MUT antibodies were identified in maternal plasma and neonatal eluates, with a high monocyte index observed in functional testing using paternal and GP.Mur-positive RBCs. Sequencing demonstrated the presence of the GYPA*19 (GYPA*Hut) allele in both infants. The two neonates had favorable outcome after exchange transfusion and intensive phototherapy. A third pregnancy was closely monitored. Anti-MUT antibodies remained stable at 1/32 between 20 and 36 WG. The patient delivered a healthy newborn without anemia. After birth, the child was tested GP.Hut negative. Conclusion: This case supports the pathogenicity of anti-MUT as a cause of severe HDFN. It underscores the diagnostic challenges posed by antibodies against LPAs and highlights the importance of extended serological, molecular, and functional testing. Crossmatching maternal plasma with paternal RBCs and systematic evaluation of serological discrepancies can reveal otherwise undetectable alloantibodies. Early identification, functional assessment, and multidisciplinary management are key to optimizing outcomes in pregnancies complicated by rare RBC alloimmunization. Anti-MUT should be considered a clinically significant antibody with the potential to cause severe HDFN, warranting proactive perinatal surveillance.
Gavillet et al. (Mon,) studied this question.