CHAPLE Disease: Understanding a Rare Complement Disorder

Introduction

CHAPLE disease, or CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy, is an ultra-rare genetic disorder that has only recently been identified and characterized. This condition affects fewer than 100 children and young adults worldwide, making it a challenge for both diagnosis and treatment. In this article, we'll explore the causes, symptoms, and latest advancements in managing this complex disorder.

What is CHAPLE Disease?

CHAPLE disease is caused by mutations in the CD55 gene, which leads to a deficiency of the CD55 protein. This protein plays a crucial role in regulating the complement system, a part of our immune defense. Without proper regulation, the complement system becomes overactive, leading to a cascade of harmful effects throughout the body, particularly in the gastrointestinal tract.

Symptoms and Clinical Presentation

The core symptoms of CHAPLE disease, as reported by Litcher-Kelly et al. (2024), include:

• Abdominal pain (experienced by ≥90% of patients)
• Diarrhea
• Facial and peripheral edema
• Nausea and vomiting

Additionally, patients may experience protein-losing enteropathy, leading to malnutrition and growth delays. In severe cases, angiopathic thrombosis can occur, potentially causing life-threatening complications.

Diagnosis

Diagnosing CHAPLE disease can be challenging due to its rarity and the similarity of its symptoms to other gastrointestinal disorders. However, advances in genetic testing have made identification more accessible. According to Ozen et al. (2017), the diagnosis is confirmed through:

1. Genetic testing to identify mutations in the CD55 gene
2. Flow cytometry or western blot analysis to confirm CD55 protein deficiency
3. Clinical presentation of characteristic symptoms

Treatment Advancements

Recent breakthroughs in treatment have dramatically improved the outlook for patients with CHAPLE disease. Ozen et al. (2021) reported significant success using eculizumab, a complement C5 inhibitor. This treatment led to:

• Cessation of gastrointestinal pathology
• Restoration of normal immunity and metabolism
• Renormalization of immunoglobulin concentrations
• Re-establishment of a healthy gut microbiome

More recently, Ozen et al. (2024) conducted a study on pozelimab, another complement inhibitor. The results were equally promising, with all patients showing serum albumin normalization and improvement in clinical outcomes after treatment.

Living with CHAPLE Disease

While CHAPLE disease is a serious condition, proper management can significantly improve quality of life. Patients and caregivers should:

• Work closely with a multidisciplinary medical team
• Adhere to prescribed treatments and follow-up schedules
• Monitor for signs of complications or disease progression
• Participate in support groups or connect with other affected families

Conclusion

CHAPLE disease, though rare, represents a significant breakthrough in our understanding of complement-mediated disorders. The identification of effective treatments like eculizumab and pozelimab offers hope to patients who previously had limited options. As research continues, we can expect further improvements in diagnosis, treatment, and quality of life for those affected by this challenging condition. For individuals experiencing unexplained gastrointestinal symptoms, especially when accompanied by edema or thrombotic events, considering CHAPLE disease in the differential diagnosis could be life-saving.