CHAPLE-Like Enteropathy and Renal Microangiopathy in an Adult Patient With CD46 Deficiency.
Bircan Erden, Pelin Korkmaz, Halil Yazici et al.
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Case in brief
A 23-year-old woman with childhood-onset enteropathy and hypogammaglobulinemia had been treated with immunoglobulin replacement for presumed common variable immunodeficiency. Duodenal biopsy showed intestinal lymphangiectasia; kidney biopsy showed chronic thrombotic microangiopathy with PLA2R-negative membranous nephropathy. C3 and C4 were normal. Sequencing found homozygous CD46 c.565T>G (p.Tyr189Asp), reported as a variant of uncertain significance; family segregation and published functional evidence supported its relevance, but patient-specific functional confirmation was unavailable. Eculizumab improved gastrointestinal symptoms and intake; after dose escalation, albumin and IgG rose and proteinuria decreased.
What made this case unusual
The CHAPLE-like enteropathy and hypogammaglobulinemia occurred with renal microangiopathy in an adult with a CD46 variant, despite normal C3 and C4. The variant remained classified as uncertain by the diagnostic laboratory.
Diagnostic / clinical pearl
In a CHAPLE-like presentation, consider CD46-associated disease when enteric protein loss and hypogammaglobulinemia coexist with renal microangiopathy, even if C3 and C4 are normal. Documented protein loss should prompt reassessment of presumed primary antibody deficiency.