Background: CHAPLE syndrome (Complement Hyperactivation, Angiopathic Thrombosis, and Protein-Losing Enteropathy) is an extremely rare and life-threatening monogenic disease caused by loss-of-function mutations of CD55 leading to dysregulation of the alternative complement pathway. The clinical pattern characterized by PLE and chronic inflammatory disease is frequently misattributed to idiopathic bowel disease (IBD) with consequent inappropriate and prolonged treatment with immunosuppressive drugs. Methods: We report on a 6-year-old boy with early-onset chronic diarrhea, failure to thrive and steroid-dependent PLE that was initially identified as IBD. To resolve the diagnostic confusion, a fulminant biochemical and genetic lookups were performed. Results: This patient's sustained biochemical abnormalities severe hypoalbuminemia (15-22 g/L), profound thrombocytosis (platelets> 800 x 10⁹/l) and dimorphic anaemia were unrelated to traditional IBD. Genetic central sequencing demonstrated a homozygous deleterious CD55 variant, confirming the diagnosis of CHAPLE syndrome. This diagnosis provided the pathophysiological explanation for complement activation. Discussion: Treatment was consequently changed from corticosteroids to pozelimab, a complement C5 inhibitor monoclonal antibody. This therapy resulted in a prompt normalization of serum albumin and relief from gastrointestinal symptoms with subsequent prolonged clinical remission. Conclusions: We report a case, which highlights that a particular combination of biochemical aberrations in a previously well individual with refractory IBD should bring to mind monogenic causes including CHAPLE syndrome. Genetic testing is the best and most accurate way to diagnose a disorder. It is a revolution in the treatment of disease: away from nonspecific suppression of the immune system and toward targeted biologic therapy aimed at its precise cause — with dramatically better outcomes. Identification of these patterns and advising on confirmatory testing is a responsibility of clinical biochemists.