Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients

Background: Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD. Aim: As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls. Methods: Appendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area. Results: Ganglionic density was 10.13 per mm² in controls versus 5.01 per mm² in FD (p<0.05). Neuronal density was 70.12 per mm² in controls, compared with 22.09 per mm² in FD (p<0.01). The other parameters were not different between the two groups. Conclusion: Densities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.