A PIGG congenital disorder of glycosylation ( PIGG ‐ CDG ) variant associated with an Emm− red blood cell phenotype in a pediatric patient

BACKGROUND: The high-prevalence Emm antigen is an epitope on the GPI (glycosylphosphatidylinositol) glycolipid backbone, which anchors proteins to the cell surface. Inherited loss-of-function of PIGG (or PIGO) results in the rare Emm- red cell (RBC) phenotype and is associated with congenital disorders of glycosylation (CDG). Anti-Emm has been reported to cause clinically significant hemolytic transfusion reactions. CASE PRESENTATION: We describe a 2-year-old male with neurologic manifestations of CDG in whom whole-exome sequencing (WES) identified a homozygous PIGG c.1515G>A, p.(Trp505Ter) variant. The patient had received a single RBC transfusion in infancy with no detectable alloantibodies. Serologic evaluation demonstrated an Emm- RBC phenotype. Confirmation by Sanger sequencing verified homozygosity for this PIGG loss-of-function variant, and family studies showed both parents and a sibling were heterozygous. DISCUSSION: To date, eight other PIGG variants are known to underlie the Emm- phenotype; the c.1515G>A, p.(Trp505Ter) variant has not previously been shown to cause a null phenotype. Recognition of the rare Emm- phenotype in patients with CDG has important transfusion implications, including alloimmunization risk and difficulty sourcing compatible blood due to the rare occurrence and lack of typing reagents. CONCLUSION: This case expands the number of PIGG variants associated with the Emm- phenotype and underscores the importance of integrating the growing number of genomic diagnostic findings with transfusion medicine evaluation to guide safe transfusion management.