Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis associated with Glu89Gln Mutation

Abstract

Aims: In the current study we aimed to explore the prevalence of gastrointestinal (GI) manifestations in hereditary transthyretin amyloid (hATTR) amyloidosis associated with Glu89Gln mutation.
 Methods: We recruited 78 patients with hATTR amyloidosis associated with Glu89Gln mutation. The diagnosis of hATTR was defined by a documented transthyretin mutation through DNA analysis. Symptoms were recorded as present or absent at the time of enrollment into the study. The gastrointestinal (GI) symptoms checklist included the following items: early satiety, nausea, vomiting, constipation, alternating diarrhea/ constipation, diarrhea, fecal incontinence and unintentional weight loss.
 Results: Forty-two patients (53.8%) reported at least one GI symptom or sign. Diarrhea was the most frequently reported (30.8%), followed by unintentional weight loss (28.2%) and nausea (21.8%). Fecal incontinence (3.8%) was the least common one. No significant gender related difference in overall GI symptom prevalence was found (females 52.16%, males 55%, p = 0.834). Type of disease onset was not related to GI prevalence (earlyonset 50%, late-onset 55.6%, p=0.650). After dividing the patients into groups with a disease duration of <5 years, 5–10 years and >10 years, respectively, the prevalence of GI symptoms was found to be significantly higher in later stages (26.3% vs. 55.0% vs. 78.9%, p = 0.005; OR 2.450, 95% CI 1.084-5.538). Gastrointestinal manifestations had no impact on survival (p=0.193).
 Conclusions: Gastrointestinal manifestations are very common in hATTR patients with Glu89Gln mutation and increase with disease duration. They are not associated with gender and onset of the disease and have no impact on patient survival. These results highlight the importance of a thorough evaluation of the GI function in patients with ATTR amyloidosis and should stimulate further studies on the phenotypic differences related to genotype and geographic origin.

Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis: a Single-Centre Experience

“…Prevalence of GI symptoms in our cohort was 82%, resulting higher than prevalence reported in the largest analysis formulated based on data from THAOS registry (59%) [7], and then prevalence observed in the general population (25-30%) [16]. Probably, our study, being based on targeted questions, could overestimate the prevalence of GI symptoms while a registry study, such as THAOS, could underestimate their prevalence, considering that the registration procedure is not identical across sites, and many different specialists may be involved.…”

“…Gastrointestinal symptoms are generally common in hereditary ATTRv amyloidosis and often occur early after disease onset [7]; our results confirm this data. Early recognition of GI dysfunction is important to enable prompt treatment to relieve symptoms, preserve quality of life, and prevent malnutrition [16]. Diagnostic tools for GI abnormalities are still limited, so currently self-reported symptoms are widely accepted measures for monitoring GI involvement in hereditary ATTRv amyloidosis [7,8,16].…”

“…The origin of this symptom is unclear and it is probably multifactorial. It is generally suggested that one of the contributing factors could be the presence of motility disturbances of the GI tract caused by an autonomic neuropathy [16]. Other factors could be malabsorption of fat and bile acids, as well as the frequent presence of bacterial overgrowth of the small bowel [16].…”

Intestinal amyloidosis: Clinical manifestations and diagnostic challenge

“…Described in 11-46% of patients, chronic diarrhea is one of the most common symptoms of intestinal amyloidosis. 8,9,13,15 In patients with unexplained diarrhea, weight loss, malabsorption, or protein loss, amyloidosis must be considered. The clinical experience of patients is not characteristic but usually the diarrhea is prolonged (longer than 4 weeks), postprandial, and may be accompanied by fecal incontinence or malnutrition.…”

“…Moreover, they suffer from abdominal pain, early satiety, nausea, vomiting, diarrhea, fecal incontinence, constipation, and gastrointestinal bleeding. 13,14 Therefore, it is important that both general practitioners (GPs) and gastroenterologists need to include amyloidosis in their diagnostic workup for disease confirmation and more effective treatment.…”