Fabry disease – a multisystemic disease with gastrointestinal manifestations

Abstract

Nonspecific gastrointestinal (GI) symptoms, such as postprandial cramping pain, diarrhea, nausea and vomiting are typical symptoms for irritable bowel syndrome or inflammatory bowel disease, but may also be the first symptoms of Fabry disease (FD). This review focus on GI manifestations in FD, by providing an overview of symptoms, a proper diagnosis, an appropriate management by FD-specific and concomitant medications and lifestyle interventions. We provide comprehensive literature-based data combined with personal experience in the management of FD patients. Since FD is rare and the clinical phenotype is heterogeneous, affected patients are often misdiagnosed. Consequently, physicians should consider FD as a possible differential diagnosis when assessing unspecific GI symptoms. Improved diagnostic tools, such as a modified GI symptom assessment scale can facilitate the diagnosis of FD in patients with GI symptoms of unknown cause and thus enable the timely initiation of a disease-specific therapy. Expansive intravenous enzyme replacement therapy with α-galactosidase A or oral chaperone therapy for patients with amenable mutations improve the disease burden including GI symptoms, but a timely start of therapy is crucial for the prognosis. A special diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) or pro- and prebiotics might improve FD-typical GI symptoms. Furthermore, preliminary success was reported with the oral administration of α-galactosidase A. In addition to a timely initiation of FD-specific therapy, affected patients with GI symptoms might benefit from a FODMAP-low diet, pro- and prebiotics and/or low-cost oral substitution with AGAL to support digestion and reduce dysbiosis.

Fabry Disease in Slovakia: How the Situation Has Changed over 20 Years of Treatment

“…We expect it will help us to monitor all FD patients, particularly children (mainly boys) and women who are waiting for correct therapy initiation and for better follow-ups with treated men. Increased attention is given to gastrointestinal symptoms and to neuropathic pain, representing early signs of FD [ 10 , 64 ].…”

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

“…The most common manifestations are abdominal pain and diarrhoea, followed by constipation, nausea, and vomiting [ 7 ]. These symptoms often appear in childhood and can be life-threatening, with a significant impact on quality of life [ 5 , 7 , 8 ].…”

“…Abdominal pain is the most frequent symptom, manifested by colic with pain in the mid or lower abdomen, bloating, cramping, or midabdominal discomfort [ 7 , 9 ]. These signs may increase during or after meals or be triggered by stress, but FD patients do not show significant differences in body mass index (BMI) due to a reduced food intake related to GI symptoms [ 7 , 10 ].…”

“…Some drugs, including loperamide, metoclopramide, proton pump, and simethicone for flatulence and bloating seem to be useful in some GI manifestations [ 7 , 13 , 14 ]. Several therapies typically used to treat Irritable Bowel Syndrome (IBS) have been proposed, such as linaclotide against constipation or, with caution in cardiac unstable conditions, antispasmodic dicyclomine against spasms [ 7 , 15 , 16 ].…”

“…Since many FODMAPs require AGAL to be digested, FD patients appear potentially responsive to this dietary protocol [ 7 , 9 , 21 ]. It usually consists of two different phases: 4–6 weeks of elimination phase on a low- FODMAP diet, followed by a gradual reintroduction phase of FODMAP-rich foods in order to define which ones are tolerated or not [ 17 , 18 ].…”