A case study recently published in Neuropediatrics described a newborn with concurrent hemolytic disease of the fetus and newborn (HDFN) and spinal muscular atrophy (SMA) who was successfully treated with onasemnogene abeparvovec.
This appears to be the first description in the literature of a presymptomatic infant with SMA who was diagnosed with alloimmune HDFN as well. In this infant, the presence of HDFN was linked to the development of hemolytic anemia and neonatal jaundice.
Following a full-term pregnancy that was deemed uneventful, a 21-year-old woman delivered a male infant. Prenatally, it was confirmed that the baby harbored the exon seven deletion of the SMN1 gene, along with three SMN2 copies. Notably, three family members had a history of SMA.
After he was born, the baby was admitted to the neonatal intensive care unit because of jaundice and underwent phototherapy. Autoimmune hemolytic was suspected because of red blood cell (RBC) fragments, target cells, and mild poikilocytosis—abnormally shaped RBCs—on a peripheral blood smear.
Negative findings on both direct and indirect Coombs tests were reported in the mother and the child.
Read more about testing and diagnosis of HDFN
Infant treated with onasemnogene abeparvovec
In some centers in which newborns with presymptomatic SMA undergo treatment, onasemnogene abeparvovec is the therapy of choice. Onasemnogene abeparvovec is an AAV-based gene replacement therapy that delivers the SMN1 gene into the anterior horn cells of the spinal cord.
Of note, at seven days prior to administration of the onasemnogene abeparvovec infusion, the newborn’s hemoglobin level stabilized, his total bilirubin concentration decreased and his direct bilirubin level remained slightly elevated.
Ultimately, the child underwent an onasemnogene abeparvovec infusion at 42 days of age, which he tolerated well. At his last follow-up visit at four months after the infusion, his hemoglobin level had increased to 12 g/dL.
All corticosteroid therapy was discontinued in the child. Based on laboratory testing, signs of hemolysis were no longer observed in the baby.
At five months after receiving onasemnogene abeparvovec, the patient’s gross motor milestone development was deemed normal for his age. His motor, language and social skills were all within what is considered acceptable for his age.
The authors noted that this case established the safety of onasemnogene abeparvovec in a newborn with HDFN. “Further studies are needed to validate the safety of [onasemnogene abeparvovec] in this subset of SMA patients utilizing the existing neonatal SMA registries,” they concluded.
