The effects of prenatal genetic analysis on fetuses born to carrier mothers with primary immunodeficiency diseases.

OBJECTIVE: Prenatal genetic analysis in primary immunodeficiency diseases (PIDs) can decrease morbidity and mortality.

METHODS: We compared the postnatal prognoses of index cases and their subsequent sibling-fetuses using prenatal genetic analysis.

RESULTS: From 2007 to 2014, 14 sibling-fetuses receiving a prenatal diagnosis born to four mothers with WAS, three with X-CGD, and one each with IPEX, XLA and severe combined immunodeficiency [RAG2-SCID] were recruited. There were six affected, two carriers, and six wild types. Among the six affected, four [3X-CGD and 1RAG2-SCID] were terminated and two [1WAS and 1X-CGD] with early prophylactics underwent successful hematopoietic stem cell transplantation (HSCT) without infection. In the 12 index cases with a postnatal diagnosis, eight died (five due to infections and one each due to refractory bleeding, severe diarrhea, and post-transplant pneumothorax), two X-CGD underwent reconstituted HSCT after recurrent life-threatening infections, one WAS developed malignancy, and another WAS developed autoimmune disorders despite the administration of prophylactics and regular immunoglobulin infusion.

CONCLUSION: Instead of recurrent life-threatening infections leading to mortality in the postnatal diagnosis group, the severe PIDs who received early prophylactics were cured by HSCT, and all of mortality were terminations in the prenatal diagnosis group. Further large-scale studies are needed to validate this beneficial effect. Key message Prenatal genetic analysis in fetuses born to PIDs carrier mothers allows for the affected fetuses to receive optimal management including prophylactics against infections and HSCT if indicated. Patients with PIDs diagnosed postnatally who are prone to severe infections have higher rates of morbidity and mortality than their subsequent siblings who have a prenatal genetic diagnosis.