Clinical and single-cell sequencing characteristics of adult-onset intestinal hypoganglionosis: a case report

Hypoganglionosis (HG) is a rare motility disorder characterized by a significant reduction in enteric ganglion cells. Its clinical presentation resembles Hirschsprung’s disease, but its pathogenesis remains unclear. The features of its immune microenvironment at single-cell resolution are rarely reported. This study included a 61-year-old male patient with pathologically confirmed focal HG. Tissue from the lesioned left hemicolon, autologous right hemicolon control tissue, and normal left hemicolon tissue were collected. These tissues were analyzed using single-cell RNA sequencing (scRNA-seq), yielding a total of 18,931 cells. Clustering, differential expression, and pathway enrichment analyses were performed to characterize the cellular composition and transcriptomic profile of HG colonic tissue. The case study revealed a classic dilated-narrowed-dilated pathological pattern in the patient’s colon, with a marked reduction in myenteric ganglion cells in the narrowed segment. scRNA-seq indicated immune microenvironment remodeling in the lesioned bowel segment, characterized by an increased proportion of plasma cells. These plasma cells exhibited features of endoplasmic reticulum stress, activation of the unfolded protein response (UPR) pathway, and enrichment in immune regulatory functions. B cells and T cells also showed enrichment in immune-related pathways. This study demonstrates that adult-acquired HG is associated with significant immune microenvironment remodeling. The findings suggest that abnormal plasma cell activation in Acquired hypoganglionosis (AHG) may initiate remodeling of metabolic and stress pathways. This could synergistically amplify the local inflammatory response through humoral and cellular immunity, and the resulting immune microenvironment may contribute to enteric neuronal damage and loss.