Amyloid Neuropathies, Familial/drug therapy* ; Benzoxazoles ; Humans ; Prealbumin

Amyloid Neuropathies, Familial/genetics* ; Humans ; Prealbumin/genetics*

Amyloid Neuropathies, Familial ; Cardiomyopathies ; Humans

Amyloid Neuropathies, Familial ; Humans

Amyloid Neuropathies, Familial/diagnosis* ; Cardiomyopathies/diagnosis* ; Humans ; Prealbumin

Amyloid ; Amyloid Neuropathies, Familial/genetics* ; China ; Humans ; Mutation ; Prealbumin/genetics*

BACKGROUND AND PURPOSE: Tafamidis functions to delay the loss of function in transthyretin familial amyloid polyneuropathy (TTR-FAP), which is a rare inherited amyloidosis with progressive sensorimotor and autonomic polyneuropathy. This systematic literature review and meta-analysis evaluated the efficacy and safety of tafamidis in TTR-FAP patients, with the aim of improving the evidence-based medical evidence of this treatment option for TTP-FAP. METHODS: A systematic search of the English-language literature in five databases was performed through to May 31, 2018 by two reviewers who independently extracted data and assessed the risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: The meta-analysis identified six relevant studies. The tafamidis group showed smaller changes from baseline in the Neuropathy Impairment Score–Lower Limbs [mean difference (MD)=−3.01, 95% confidence interval (CI)=−3.26 to −2.75, p < 0.001] and the Norfolk Quality of Life-Diabetic Neuropathy total quality of life score (MD=−6.67, 95% CI=−9.70 to −3.64, p < 0.001), and a higher modified body mass index (MD=72.45, 95% CI=69.41 to 75.49, p < 0.001), with no significant difference in total adverse events [odds ratio (OR)=0.69, 95% CI=0.35 to 1.35, p=0.27]. The incidence of adverse events did not differ between tafamidis and placebo treatment except for fatigue (OR=0.13, 95% CI=0.02 to 0.72, p=0.02) and hypesthesia (OR=0.16, 95% CI=0.03 to 0.92, p=0.04). CONCLUSIONS: This systematic review and meta-analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life. The rates of adverse events did not differ between the patients in the tafamidis and placebo groups. Tafamidis might be a safer noninvasive option for patients with TTR-FAP.
Amyloid Neuropathies ; Amyloid Neuropathies, Familial* ; Amyloidosis ; Bias (Epidemiology) ; Body Mass Index ; Extremities ; Fatigue ; Humans ; Hypesthesia ; Incidence ; Nutritional Status ; Polyneuropathies ; Population Characteristics ; Prealbumin* ; Publication Bias ; Quality of Life

BACKGROUND/AIMS: The gastrointestinal (GI) tract often becomes involved in patients with systemic amyloidosis. As few GI amyloidosis data have been reported, we describe the clinical features and outcomes of patients with pathologically proven GI amyloidosis. METHODS: We identified 155 patients diagnosed with systemic amyloidosis between April 1995 and April 2013. Twenty-four patients (15.5%) were diagnosed with GI amyloidosis using associated symptoms, and the diagnoses were confirmed by direct biopsy. RESULTS: Among the 24 patients, 20 (83.3%) had amyloidosis light chain (AL), three (12.5%) had amyloid A, and one (4.2%) had transthyretin-related type amyloidosis. Their median age was 57 years (range, 37 to 72), and 10 patients were female (41.7%). The most common symptoms of GI amyloidosis were diarrhea (11 patients, 45.8%), followed by anorexia (nine patients, 37.5%), weight loss, and nausea and/or vomiting (seven patients, 29.2%). The histologically confirmed GI tract site in AL amyloidosis was the stomach in 11 patients (55.0%), the colon in nine (45.0%), the rectum in seven (35.0%), and the small bowel in one (5.0%). Patients with GI involvement had a greater frequency of organ involvement (p = 0.014). Median overall survival (OS) in patients with GI involvement was shorter (7.95 months; range, 0.3 to 40.54) than in those without GI involvement (15.84 months; range, 0.0 to 114.53; p = 0.069) in a univariate analysis. A multivariate analysis of prognostic factors for AL amyloidosis revealed that GI involvement was not a significant predictor of OS (p = 0.447). CONCLUSIONS: The prognosis of patients with AL amyloidosis and GI involvement was poorer than those without GI involvement, and they presented with more organ involvement and more advanced disease than those without organ involvement.
Adult ; Aged ; Amyloid Neuropathies, Familial/*diagnosis/immunology/mortality/pathology/therapy ; Biomarkers/analysis ; Biopsy ; Female ; Gastrointestinal Diseases/*diagnosis/immunology/mortality/pathology/therapy ; Gastrointestinal Tract/immunology/*pathology ; Humans ; Immunoglobulin Heavy Chains/analysis ; Immunoglobulin Light Chains/analysis ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Serum Amyloid A Protein/analysis ; Time Factors

BACKGROUNDMutations of transthyretin (TTR) cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis.

METHODSClinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed.

RESULTSThe onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss of myelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2.

CONCLUSIONSSince the pathological examinations of sural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.

Adult ; Aged ; Aged, 80 and over ; Amyloid Neuropathies, Familial ; diagnosis ; genetics ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Middle Aged ; Mutation ; genetics ; Pedigree ; Prealbumin ; genetics

Amyloid Neuropathies, Familial ; genetics ; Cardiomyopathies ; Humans ; Mutation