Chronic intestinal pseudo-obstruction. Did you search for lysosomal storage diseases?

Abstract

Chronic intestinal pseudo-obstruction results in clinical manifestations that resemble intestinal obstruction but in the absence of any physical obstructive process. Fabry disease is an X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement. We report the occurrence of chronic intestinal pseudo-obstruction in two unrelated patients with Fabry disease and the possible explanation of a direct relation of these two disorders. In Fabry disease, gastrointestinal symptoms occur in approximately 70% of male patients, but the frequency ranges from 19% to 69% in different series. In some patients, colonic dysmotility due glycolipid deposition in autonomic plexus and ganglia can lead to the pseudo-obstruction syndrome, simulating intestinal necrosis. That is why up to this date colostomy has been performed in some cases, even for children with FD without cardiac, renal or cerebrovascular compromise. Early treatment with enzyme replacement therapy in asymptomatic or mildly symptomatic patients may be justified in order to prevent disease progression. Several studies have demonstrated that enzyme replacement therapy alleviates GI manifestations. Because of the non-specific nature of the gastrointestinal symptoms, diagnosis of Fabry disease is often delayed for several years. Gastrointestinal involvement is often misdiagnosed or under-reported. It is therefore very important to consider Fabry disease in the differential diagnosis of chronic intestinal pseudo-obstruction.

Altered globotriaosylceramide accumulation and mucosal neuronal fiber density in the colon of the Fabry disease mouse model

“…In fact, Gb3 accumulation leads to an impaired cellular function, such as limited contractility of muscular cells, and, in turn, to an altered expression of ion channels . Recently, chronic intestinal pseudo‐obstruction was reported in a patient group as a result of substrate deposition at autonomic ganglia and smooth muscle cell level . These alterations could trigger secondary pathological processes reflecting a tissue response (ie, hypertrophy).…”

“…17,[50][51][52][53] Recently, chronic intestinal pseudoobstruction was reported in a patient group as a result of substrate deposition at autonomic ganglia and smooth muscle cell level. 36,54 These alterations could trigger secondary pathological processes reflecting a tissue response (ie, hypertrophy). It has to be underlined that our study did not clarify whether vascular occlusion, a potential pathogenetic mechanism of FD occurring in cerebral and different additional tissues in human FD, may contribute to the abnormalities detected in the colon innervation.…”

Non-specific gastrointestinal features: Could it be Fabry disease?

“…Other GI disor- ders include haemorrhoids (adults, not children), gastritis or ulcer and pancreatitis [5]. Chronic intestinal pseudo-obstruction [34,35], diverticular disease [10,[36][37][38], and bowel ischaemia [32,35] have also been reported.…”

“…Dysfunction of the autonomic nervous system responsible for gut motility, vasculopathy affecting GI circulation, and tissue inflammation related to GL-3 accumulation seem to be the three principal mechanisms that are implicated (Fig. 2) [31,34]. Collectively, these pathological processes lead to changes such as a rapid gut transit time, reduced peristalsis, intestinal stasis, bacterial overgrowth, malabsorption of nutrients, pancreatic insufficiency, gastroparesis (delayed emptying), and ischaemic or neuropathic damage, all of which contribute to the GI symptoms associated with Fabry disease [31,34].…”

“…Biopsies can be taken for histology studies; typically, patients with Fabry disease have tissue inflammation and normal epithelial/villous structure, with evidence of GL-3 deposits in enlarged and vacuolated neurons (Fig. 3), vascular endothelial cells, and vascular smooth muscle cells [34,38]. Gastric biopsies may reveal positive anti-GL-3 immunostaining results in vascular smooth muscle cells, endothelia, and interstitial cells, in both the classic and non-classic forms of Fabry disease, though some unclassified mutational variants may not react to immunostaining (Fig.…”