Presentation (CTI)

OBJECTIVES: CHAPLE disease (CD55-deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy) is often misdiagnosed or underdiagnosed due to its rarity and overlapping symptoms with more common conditions like protein-losing enteropathy (PLE). We aimed to identifying potential CHAPLE patients among PLE patients by analyzing their characteristic symptoms for CD55-genetic testing to confirm a CHAPLE diagnosis.
METHODS: We utilized the IMO-Health Terminology¹ Search-log to identify PLE patients PLE together with a comprehensive list of their other conditions. Additionally, we collected clinical reports of 11 confirmed CHAPLE patients from the literature² and extracted a detailed list of their conditions using a large language model. All conditions were normalized using Unified Medical Language System Concept Unique Identifiers (CUIs) for comparative and clustering analyses based on patient condition similarity using the Jaccard index.
RESULTS: We identified 243 pediatric PLE patients from IMO Search-log with 6,257 documented conditions. After normalization, we obtained 2,268 unique CUIs. Common conditions in confirmed CHAPLE patients included hypogammaglobulinemia, vitamin deficiency due to malabsorption, hypoalbuminemia, edema, anemia, chronic/recurrent diarrhea, growth retardation, lymphoid infiltrates in the mucosa, vomiting, and abdominal pain. Among PLE patients, frequent conditions were abdominal pain (51.9%), intestinal disease (47.3%), anemia (42.0%), pulmonary embolism (28.8%), hypoalbuminemia (25.9%), vitaminD deficiency (18.9%), and edema (18.1%). Based on clustering analysis, six pediatric PLE patients exhibited a high likelihood of CHAPLE, presenting with 6-8 characteristic symptoms commonly observed in confirmed CHAPLE cases, including diarrhea, hypoalbuminemia, and anemia. Additionally, 15 PLE patients exhibited 3-5 symptoms shared with CHAPLE patients, suggesting potential candidates for further investigation.
CONCLUSIONS: This proof-of-concept study demonstrates an approach to identifying potential CHAPLE cases among patients with similar symptoms, increasing the likelihood of early detection. Our approach can facilitate timely intervention by pinpointing patients for genetic testing, which is crucial for improving patient outcomes and quality of life in ultra-rare diseases.