Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy

To the Editor: Protein-losing enteropathy usually manifests as peripheral and visceral edema due to hypoalbuminemia. Disease onset was between 10 months and 3 years of age, and the patients presented with generalized edema, severe hypoalbuminemia (reaching 0.5 g per deciliter), diarrhea, and abdominal complications, with repeated thrombotic events occurring in three of them. Supportive management of the disorder with a low-fat diet and supplementation with medium-chain triglycerides only partially improved the nutritional status of the patients who adhered to the dietary regimen. Two patients died from disease complications. Additional clinical data are available in the Supplementary Appendix. Whole-exome sequencing analysis revealed a homozygous frameshift variant in CD55 (GenBank number, NM_001114752 . 1), c.43del (p.Leu15Serfs*46) (ClinVar accession number, SCV000579315). The variant segregated with the disease phenotype in the extended family; that is, only patients were homozygotic for the variant, whereas healthy family members either were heterozygotic for the variant or had the wildtype gene. Flow cytometric and hemagglutination studies revealed markedly decreased binding of CD55 antigens on patients' red cells and granulocytes, as compared with those of unaffected persons. Abnormal complement activation was observed in patients with CD55 deficiency; that is, membrane attack complex (MAC) deposition