A
PIGG
congenital disorder of glycosylation (
PIGG
‐
CDG
Alastair Murray, Connie M. Westhoff, Sunitha Vege, Hallie Lee‐Stroka, Randall W. Velliquette, William J. Lane, Jillian G. Buchan, Nabiha H. Saifee, Rida A. Hasan Abstract
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.