Examining Non-specific GI Symptoms May Hasten Diagnosis of Fabry Disease

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Prenatal Genetic Diagnosis

Gastrointestinal specialists should add Fabry disease to their list of possible causes of non-specific gastrointestinal symptoms, according to a review published in the journal Digestive and Liver Disease. The authors suggest that improved diagnostic tools for these symptoms may help the diagnosis of Fabry disease.

The recent study, “Non-specific gastrointestinal features: Could it be Fabry disease?,” summarizes the conclusions of multi-specialist discussions during an Internal Medicine Advisory Board in Rare Diseases, that took place December 2016 in Rome, Italy.

Fabry disease is a storage disorder caused by mutations in the α-galactosidase A (GLA) gene, that result in absent or markedly reduced GLA enzymatic activity. Symptoms of the disease include episodes of pain —  particularly in the hands and feet — decreased ability to sweat, clusters of small, dark red spots on the skin, cloudiness of the front part of the eye, kidney damage, and gastrointestinal problems.

Early treatment, before irreversible organ damage occurs, is key to obtain the best clinical responses. However, the diagnosis of Fabry disease is challenging, and delays and misdiagnosis often happen due to non-specific early symptoms, such as gastrointestinal symptoms.

The most common gastrointestinal symptoms in Fabry disease are abdominal cramping, bloating, diarrhea, nausea, and vomiting. They often are the first symptoms of the disease, and have been associated with a significant reduction in patients’ quality of life.

However, the exact prevalence of gastrointestinal symptoms remains unclear, as they often are underreported.

Recent data from the Fabry Outcome Survey (NCT03289065) — a global, multicenter, observational registry for patients with Fabry disease — showed that gastrointestinal symptoms were reported by 60% of children and 50% of adult women entering the registry.

Also, abdominal pain was found to be one of the most common gastrointestinal symptoms reported in Fabry disease patients, accounting for about 30% of these symptoms in all patients, and almost 50% in child patients.

The fact that these non-specific gastrointestinal symptoms may suggest more common disorders — such as irritable bowel syndrome or inflammatory bowel disease — combined with the rarity of Fabry disease, may  cause misdiagnosis and/or delay its diagnosis for several years.

The authors emphasize that Fabry disease should be considered as a possible cause of gastrointestinal problems in patients with a long history of gastrointestinal symptoms of unknown cause.

Also, the authors propose that the inclusion of Fabry disease-related questions in the Gastrointestinal Symptom Rating Scale (GSRS) could serve as a tool to help diagnosis patients with a history of unexplained gastrointestinal symptoms.

The researchers noted that potential additions to the GSRS questionnaire should be tested and validated as soon as possible, since “reducing diagnostic delays in Fabry disease and diagnosing the disease in patients as young as possible is vital in order to improve clinical outcomes through timely initiation of disease-specific treatment.”