Inherited Glycosylphosphatidylinositol Deficiency Caused by PIGW Variants With Recurrent Infections and Complement Abnormalities.

Glycosylphosphatidylinositol (GPI) serves as an anchor protein for human cells, and genetic defects in this protein can lead to inherited GPI deficiency (IGD). Intellectual disability, distinctive facial features, epilepsy, hyperphosphatasia, and multiple organ anomalies characterize IGD, with severity varying based on the affected genes. A 53-day-old male, born to nonconsanguineous parents, presented with poor feeding and fever. The patient exhibited unique facial characteristics, hyperphosphatasia, and reduced complement levels. During his 2.5-month admission, he exhibited recurrent fever and infection. Whole-genome sequencing revealed compound heterozygous variants in the PIGW gene, c.[173T>C];[617_620del], p.[Leu58Pro];[Val206Glyfs*3]. Flow cytometry indicated a marked decrease in CD16 expression on granulocytes, leading to the diagnosis of IGD in the patient. This patient exhibited persistent low complement levels (CH50, C3, and C4) alongside elevated immune complexes, which may reflect complement activation secondary to infections. Transient complement abnormalities of this kind may occasionally accompany recurrent infections in patients with GPI biosynthesis defect 11. This case broadens the phenotypic spectrum of PIGW-related IGD and highlights the importance of further research to clarify the relationship between infection, complement activation, and GPI biosynthesis.