Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis.

BACKGROUND: Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients' small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non-amyloidosis patient controls. METHODS: ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24-hour duodenojejunal manometry (n = 19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of ≥50 years were defined as late-onset cases. For each patient, three age- and sex-matched patient controls (n = 57) were selected from the total pool of investigated patients. KEY RESULTS: Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P = .01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low-amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P = .10). Furthermore, late-onset patients showed a delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not observed for early-onset patients or within the control group. CONCLUSIONS AND INFERENCES: Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non-amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late-onset patients warrants further investigation.

Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy.

BACKGROUND: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset. METHODS: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine × BMI). KEY RESULTS: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T(50) 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.02-0.52) and sympathetic dysfunction (OR 0.23, CI 0.10-0.51), but not gender (OR 0.76, CI 0.31-1.84) and parasympathetic dysfunction (OR 1.81, CI 0.72-4.56), contributed to gastric retention. CONCLUSIONS AND INFERENCES: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.