Asunto(s)
Neuropatías Amiloides Familiares/metabolismo , Axones/fisiología , Prealbúmina/genética , Adulto , Anciano , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/fisiopatología , Axones/metabolismo , Axones/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Canales de Potasio/metabolismo , Canales de Potasio/fisiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/fisiologíaRESUMEN
We report the clinical features of a patient with hereditary transthyretin (ATTR) amyloidosis associated with a novel mutation (Y114S, p.Y134S). A 65-year-old Japanese man was admitted to our hospital after a 3-year history of progressive dyspnea on exertion. Five years previously, he presented dysesthesia in both hands caused by carpal tunnel syndrome. A genetic analysis revealed a base pair substitution of adenine to cytosine in the second codon of exon 4, residue 114, in the TTR gene (c.401A>C). The clinical characteristics were progressive cardiomyopathy with a poor vital prognosis, late onset, sporadic case, bilateral carpal tunnel syndrome, hypothyroidism, and small fiber neuropathy.
Asunto(s)
Neuropatías Amiloides Familiares/genética , Cardiomiopatías/genética , Prealbúmina/genética , Anciano , Neuropatías Amiloides Familiares/fisiopatología , Síndrome del Túnel Carpiano/genética , Síndrome del Túnel Carpiano/fisiopatología , Exones , Pruebas Genéticas , Humanos , Hipotiroidismo/genética , Masculino , Mutación , Conducción NerviosaRESUMEN
Hereditary transthyretin (ATTR) amyloidosis is a life-threatening, autosomal dominant, systemic amyloidosis caused by mutant transthyretin. In addition to ATTRV30M in endemic and non-endemic areas, more than 140 non-V30M mutations occur worldwide. The aim of this study was to analyze the clinical characteristics and genetic frequencies of hereditary ATTR amyloidosis. Diagnostic results and clinical manifestations of hereditary ATTR amyloidosis from April 1, 2012, to March 31, 2017, at Amyloidosis Medical Practice Center, Kumamoto University Hospital were analyzed. One hundred and four patients received a diagnosis of symptomatic hereditary ATTR amyloidosis. The following mutations of the TTR gene and their percentages were found: V30M in endemic areas, 10.6%; V30M in non-endemic areas, 51.0%; and non-V30M, 38.5%. The ages at onset of patients with ATTRV30M amyloidosis in non-endemic areas (66.6 ± 8.7 years) and those with non-V30M ATTR amyloidosis (55.8 ± 13.6 years) were significantly higher than those with ATTRV30M amyloidosis in endemic areas (37.0 ± 12.6 years). Of patients with ATTRV30M amyloidosis in endemic and non-endemic areas, and non-V30M ATTR amyloidosis, 63.6, 66.0, and 27.5% initially presented with polyneuropathy, respectively. Of patients with ATTRV30M amyloidosis in endemic areas, 81.8% had a family history of this disease. However, a significantly smaller percentage of patients with ATTRV30M amyloidosis (30.0%) in non-endemic areas and non-V30M ATTR amyloidosis (34.0%) had a family history. Patients with ATTRV30M amyloidosis in non-endemic areas and patients with non-V30M ATTR amyloidosis occurred more frequently than previously believed, and their clinical manifestations were diverse.
Asunto(s)
Neuropatías Amiloides Familiares/epidemiología , Neuropatías Amiloides Familiares/genética , Epidemias , Mutación/genética , Prealbúmina/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Masculino , Metionina/genética , Persona de Mediana Edad , Estudios Retrospectivos , Estadísticas no Paramétricas , Valina/genética , Adulto JovenRESUMEN
The relationship between familial amyloid polyneuropathy (FAP), which is caused by mutated transthyretin (TTR), and inflammation has only recently been noted. To determine whether inflammation is present in FAP carriers and patients, serum interleukin (IL)-6 concentration in 57 healthy donors (HD), 21 FAP carriers, and 66 FAP patients was examined, with the relationship between IL-6 and TTR assessed in each group by multiple regression analysis and structural equation models (SEM). Compared with HD, IL-6 concentration was elevated in FAP carriers (p = 0.001, 95% CI 0.398-1.571) and patients (p = 0.002, 95% CI 0.362-1.521). Further, SEM indicated a positive relationship between IL-6 and TTR in FAP carriers (p = 0.010, 95% CI 0.019-0.140), but not in HD and FAP patients. In addition, we determined whether TTR induces production of pro-inflammatory cytokines ex vivo. HD-derived CD14 + monocytes and induced pluripotent stem cell-derived myeloid lineage cells from a HD and FAP patient dose-dependently produced IL-6 under mutated and aggregated TTR conditions, compared with wild-type TTR. In conclusion, FAP carriers and patients are in an inflammatory state, with the presence of mutated TTR being a trigger of inflammation, especially in FAP carriers.
Asunto(s)
Neuropatías Amiloides Familiares/genética , Inflamación/patología , Mutación/genética , Prealbúmina/genética , Adulto , Anciano , Neuropatías Amiloides Familiares/sangre , Femenino , Heterocigoto , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Análisis Multinivel , Análisis Multivariante , Células Mieloides/metabolismoRESUMEN
Kumamoto Earthquakes in 2016 severely affected medical circumstances and condition of each patient with neuro-muscular diseases, in addition to having destroyed life circumstances of local residence. Number of neuro-muscular disease patients admitted to the Department of Neurology, Kumamoto University, the only university hospital in the prefecture, increased approximately twice compared to usual years. Most of the related facilities were able to admit emergency patients with neuro-muscular diseases although the hospital buildings were damaged in various degrees. A number of issues remained unsolved as to emergency contact system, securement of emergency beds for severe neuro-muscular diseases, and information system for these patients.
