High GI symptom burden in Fabry not linked to gut motility problems

Problems may be tied to dysfunction in nerve cells that control gut reflexes

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Problems moving food through the gastrointestinal system didn’t largely account for gastrointestinal (GI) symptoms in Fabry disease patients, a recent study shows.

The symptoms, which have an impact on patients’ quality of life, may instead arise from dysfunction in the nerve cells that control gut reflexes.

The study, “Gastrointestinal sensory neuropathy and dysmotility in Fabry disease: Presentations and effect on patient’s quality of life,” was published in Clinical and Translational Gastroenterology.

People with Fabry disease are deficient in alpha-galactosidase A (Gal A), an enzyme that breaks down certain fatty molecules in cells. As a result, the molecule accumulates to toxic levels and disrupts the function of various organ systems.

GI issues are among the disease’s symptoms and may include diarrhea, constipation, abdominal pain, and nausea, among other manifestations.

How these symptoms arise isn’t known, but could be related to problems with the movement of food through the GI system and out of the body, called gut motility. Difficulty moving food because of abnormal contractions of the intestinal muscles, or gut dysmotility, may be caused by muscle weakness or by signaling changes in the nerves that control the gut.

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Doctors Underplay Impact of Fabry Symptoms on Life Quality: Study

GI symptoms and gut motility in Fabry disease

Scientists in the U.S. and Israel described the results of a clinical trial (NCT02798458) wherein they evaluated GI symptoms, gut dysmotility, and quality of life impacts among 48 Fabry disease patients (28 female, 20 male; median age, 47) who reported chronic GI symptoms.

The patients underwent a clinical interview and answered questionnaires related to GI symptoms and their impact. They also completed a wireless motility capsule study, wherein a capsule is swallowed and transmits data as it moves through the GI tract.

The most common non-GI manifestation was neurological involvement — in 95.8% of patients.

Neurological and GI manifestations were also the symptoms with the earliest age of onset, with median ages of 9 and 12, respectively. GI symptoms started significantly earlier than certain other Fabry complications, including cardiovascular problems and hearing.

Abnormal bowel habits (87.5%) and abdominal pain (81.3%) were the most commonly reported GI symptoms. Men reported higher rates and severity of diarrhea, whereas female patients had higher rates and severity of constipation and bloating, and more often had indigestion after eating and acid reflux.

Despite this high symptom burden, some type of dysmotility was seen in only 34% of the participants in the capsule study. This involved delays in transit through the stomach (gastric; 10.6%), small intestine (6.4%), and colon (21.3%). Motility issues in the small intestine were correlated with nausea/vomiting, early fullness when eating, acid reflux, and overall GI symptom burden. Problems with colon motility were significantly associated with constipation.

Some patients (38%) showed signs of an exaggerated gastrocolic reflex, or an increase in colon motility that occurs after eating, which was associated with diarrhea.

The nervous system and GI problems

The lack of dysmotility overall among the patients suggests GI symptoms may be secondary to nervous system issues, particularly given the high rate of neurological involvement in this group, according to the researchers, who noted many GI symptoms overlap with other disorders of gut-brain interactions.

A number of GI symptoms were found to impact aspects of Fabry disease patients’ lives and had links to depression, anxiety, and a loss of work productivity. Patients with fewer than three bowel movements a week had a lower quality of life than their peers across several evaluated domains.

Still, GI symptoms didn’t correlate with measures of overall Fabry disease severity, indicating, “current Fabry scores underrepresent the GI symptom effect on patients with Fabry disease,” wrote the researchers, who described their study as the largest so far to “investigate the gastrointestinal symptoms in depth while also measuring total gut motility.”

The researchers said topics for future research should be bacterial growth in the gut or the effect of medicine on GI symptoms. “While the significance of GI symptoms is clear from our findings, further research of the mechanism of GI symptoms is needed to better inform us of appropriate treatment modalities,” they said.