Genetic screening for hereditary transthyretin amyloidosis with polyneuropathy in western Sicily: Two years of experience in a neurological clinic.

BACKGROUND AND PURPOSE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. METHODS: A prospective systematic genetic screening for ATTRv-PN was proposed in patients presenting with a sensory-motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. RESULTS: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv-PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv-PN patients and 26 presymptomatic carriers) among 84 first-degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. CONCLUSIONS: A systematic screening for ATTRv-PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv-PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow-up at the clinical onset.

Gastroparesis: The Complex Interplay with Microbiota and the Role of Exogenous Infections in the Pathogenesis of the Disease.

Gastroparesis (GP) is a disorder of gastric functions that is defined by objective delayed gastric emptying in the absence of mechanical obstruction. This disease is characterized by symptoms such as nausea, post-prandial fullness, and early satiety. GP significantly impacts patients' quality of life and contributes to substantial healthcare expenses for families and society. However, the epidemiological burden of GP is difficult to evaluate, mainly due its significant overlap with functional dyspepsia (FD). GP and FD represent two similar diseases. The pathophysiology of both disorders involves abnormal gastric motility, visceral hypersensitivity, and mucosal inflammation. Moreover, both conditions share similar symptoms, such as epigastric pain, bloating, and early satiety. The latest evidence reveals that dysbiosis is directly or indirectly connected to gut-brain axis alterations, which are the basis of pathogenesis in both FD and GP. Furthermore, the role of microbiota in the development of gastroparesis was demonstrated by some clinical studies, which found that the use of probiotics is correlated with improvements in the gastric emptying time (GET). Infections (with viruses, bacteria, and protozoa) represent a proven etiology for GP but have not been sufficiently considered in current clinical practice. Previous viral infections can be found in about 20% of idiopathic GP cases. Moreover, delayed gastric emptying during systemic protozoal infections represents a huge concern for compromised patients, and few data exist on the topic. This comprehensive narrative review analyzes the relationship between microorganisms and GP. We explore, on the one hand, the correlation between gut microbiota dysbiosis and GP pathogenesis, including treatment implications, and, on the other hand, the association between exogenous infections and the etiology of the disease.