Abstract
BACKGROUND: Inflammatory bowel disease (IBD) is a heterogeneous group of disorders associated with environmental triggers and dysregulated immune responses resulting in chronic, recurrent intestinal inflammation. Very early-onset IBD (VEO-IBD) refers to patients with symptoms or diagnosis before the age of 6 years and is widely thought to be associated with monogenic mutations. Traditional drug therapy is often ineffective in this patient population, while hematopoietic stem cell transplantation (HSCT) represents the definitive cure for patients with gene mutations. CASE PRESENTATION: We report a case of VEO-IBD associated with a monogenic mutation in a 2-year-old girl presenting mainly with gastrointestinal symptoms, including recurrent hematochezia and abdominal pain for more than 3 months. A gastroscopy revealed erosive gastritis and bulbar duodenitis, while a colonoscopy indicated erosive colitis. Abnormal results were obtained from the dihydrohodamine (DHR) assay and immunoglobulin testing. Whole-exome sequencing identified a heterozygous and de novo nonsense mutation (c.388 C > T; p.R130X) in the CYBB gene leading to deficiency of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) (encoded by CYBB), a critical component of phagocytes. HSCT was performed successfully, and the DHR assay showed that normal neutrophil function was restored. Six months after HSCT, clinical remission was observed, and a repeat colonoscopy revealed intestinal mucosal healing was attained. CONCLUSIONS: Patients with CYBB mutations often develop recurrent or severe bacterial or fungal infections, mostly in the lungs, skin, lymph nodes, and liver. Here, we report on a young female child with CYBB mutations presenting predominantly with gastrointestinal symptoms. This study explores the mechanisms of inflammatory bowel disease caused by a monogenic mutation in CYBB to improve early diagnosis and effective treatment rates of this patient population.