A significant breakthrough in understanding rare diseases has been made by researchers from the Cliniques universitaires Saint-Luc and the Institut de Duve of UCLouvain. They have discovered a new pancreatic pathology associated with rare genetic disorders that can affect digestion and nutrition. This finding, published in the scientific journal GUT, offers encouraging prospects for patient management and the development of future therapeutic strategies.
Ciliopathies, caused by malfunctions of 'primary cilia' that act as cellular communication antennae, are rare genetic conditions. While kidney and liver damage are well-documented, the involvement of the pancreas was previously unknown. The research conducted in Brussels has shed light on this connection, revealing consequences for digestion and nutrition.
The study is the result of a collaboration between the Institut de Duve of UCLouvain, an expert in ciliopathy mechanisms, and pediatric gastroenterologist clinicians from the Cliniques universitaires Saint-Luc. The latter had observed unexplained symptoms in some patients, particularly pancreatic abnormalities associated with kidney problems. The project was supported by the FNRS, the Fondation contre le cancer, the Fondation Roi Baudouin, and the Fondation Saint-Luc.
The analysis of a cohort of 350 pediatric patients revealed mutations in genes related to primary cilia (HNF1B and NPHP3) in some patients suffering from kidney issues. Subsequent animal modeling using genetically modified mice highlighted progressive atrophy of pancreatic acinar cells and fat accumulation, a pathological mechanism termed 'adipopancreatosis'.
These findings were validated in humans through a specific MRI technique. This allowed for the measurement of significantly higher pancreatic fat content in patients carrying HNF1B or NPHP3 mutations, confirming the existence of adipopancreatosis in humans.
This discovery opens the door to systematic screening of exocrine pancreatic function in carriers of ciliopathy-related mutations, especially those with unexplained digestive symptoms. Early detection could prevent nutritional complications, particularly in patients with kidney disease. In the long term, these findings may lead to targeted therapies to treat pancreatic and kidney damage.
