Gastrointestinal Manifestations and Low-FODMAP Protocol in a Cohort of Fabry Disease Adult Patients

Abstract

Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme deficiency. Gastrointestinal (GI) manifestations are reported in FD with a prevalence of about 50%, usually treated by Enzymatic Replacement Therapy (ERT) or oral treatment. Since FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) can be involved in GI manifestations and dysbiosis in FD patients, a low-FODMAP diet could represent an alternative adjunctive treatment in FD subjects, as well as being useful for reducing symptoms in Irritable Bowel Syndrome (IBS). We retrospectively assessed data from 36 adult FD patients followed at the Inherited Metabolic Rare Diseases Adult Centre of the University Hospital of Padova (mean age 47.6 ± 16.2 years). Patients were screened for GI symptoms by IBS severity score and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires. In symptomatic patients, the low-FODMAP diet was proposed in order to improve GI manifestations; it consists of a phase of elimination of fermentable saccharides, succeeded by a gradual reintegration of the same. Severe or moderate GI symptoms were found in 61.1% of patients, with no correlation to the therapy in use, and significantly more severe in the classical form of FD. The protocol was completed by seven patients affected by severe GI manifestations, significantly higher than the others. The low-FODMAP diet significantly improved indigestion, diarrhoea, and constipation. This dietetic protocol seemed to have a positive impact on intestinal symptoms, by identifying and reducing the intake of the foods most related to the onset of disorders and improving the clinical manifestations. A low-FODMAP diet may be an effective alternative approach to improve intestinal manifestations and quality of life, and nutrition can play an important role in the multidisciplinary care of patients with FD.

Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease

“…The same scenario might arise in FD patients, as well as in the animal model of the disease. Indeed, a recent retrospective analysis revealed that a low-FODMAP diet can significantly improve GI manifestations, like indigestion, diarrhea, and constipation in FD patients 85 . FD-related symptoms might therefore benefit from either reduction of galacto-oligosaccharides or their proper digestion.…”

Increased Soluble Interleukin 6 Receptors in Fabry Disease

“…In this putative scenario, the activation of IL-6 soluble receptors, able to spread inflammatory signals all over the body, might in part explain some of the clinical presentations of FD, which feature multisystemic damage, also involving tissues not directly affected by Gb3 accumulation, as, for instance, the gastrointestinal system [ 23 , 24 ] or the bone [ 25 , 26 ]. Our data provide further evidence that other biological processes, besides the cellular alterations associated with Gb3 deposition, might participate in the irreversible tissue and organ damage featured in FD, similar to what was found, for instance, in the development of kidney fibrosis in FD [ 7 ].…”

Diet and Physical Activity in Fabry Disease: A Narrative Review

“…In general, FODMAPs are a broad class of small carbohydrates containing only 1-10 sugars, generally found in a range of very common and diverse foods (Table 1) [59]. They are also classified into four main groups depending on the length of the carbohydrate chain and intestinal fermentation processes [60,61]. Among the oligosaccharides, we find fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) present in wheat and rye-based products, legumes, nuts, artichokes, onions, and garlic.…”

“…The dietary protocol in question consists of two different phases: the first generally lasts 4-6 weeks and involves the total elimination of foods containing FODMAPs, while the second consists of the progressive consumption of small quantities of foods containing FODMAPs [61].…”