Amyloid Neuropathies, Familial ; Humans

Amyloid Neuropathies, Familial ; Cardiomyopathies ; Humans

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

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

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

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

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

A 53-year-old man complained of orthostatic, non-rotating dizziness, and chronic watery diarrhea of several years duration. His nerve-conduction velocity test revealed peripheral sensory-motor polyneuropathy and he showed an autonomic function abnormality. Echocardiographic examination showed ventricular and atrial wall thickening with a granular "sparkling" appearance. Left ventricular systolic function was preserved but pseudonormal diastolic dysfunction was present. Coronary angiography showed normal coronary arteries and an endomyocardial biopsy revealed lesions consistent with cardiac amyloidosis. Colonoscopic biopsy also revealed the deposition of amyloid fibrils. Gene analysis found the transthyretin variant Asp38Ala. His son had same mutation, but three daughters did not. In conclusion, we report a case of familial transthyretin amyloidosis with Asp38Ala.
Amyloid ; Amyloid Neuropathies, Familial ; Amyloidosis ; Biopsy ; Coronary Angiography ; Coronary Vessels ; Diarrhea ; Dizziness ; Hypotension, Orthostatic ; Nuclear Family ; Polyneuropathies ; Prealbumin

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

OBJECTIVETo study the clinical and genetic features of familiar amyloid polyneuropathy (FAP).

METHODSThree families of suspected FAP in China mainland and Macau were investigated on aspects of clinical manifestations, histological features, and gene analysis.

RESULTSAll the 3 families had the clinical features of sensory and motor polyneuropathies, and notable vegetative nerve involvements. Affected cases of one family had ultrasound proved cardiomyopathy. Histological studies showed amyloid deposition in all the biopsy tissues of the affected cases of the 3 families, and anti-transthyretin antisera staining was positive in 3 cases of one family. Gene analysis confirmed that mutation types were amyloidogenic transthyretin (ATTR) Val30Met, Phe33Val, and Gly67Glu in the 3 families respectively. The ATTR Gly67Glu family had a shorter survival time due to the heart involvement compared with the other 2 families.

CONCLUSIONFAP is an autosomal dominant inherited disease, with its clinical manifestations related to the type of genetic mutation.

Adult ; Amyloid Neuropathies, Familial ; genetics ; pathology ; China ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Prealbumin ; genetics