Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan - Clinicopathological and genetic features
Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan - Clinicopathological and genetic features
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DOI：
10.1093/brain/122.10.1951
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发表时间：
1999-10-01
期刊：
影响因子：
14.5
通讯作者：
Sobue, G
中科院分区：
文献类型：
--
作者：
Misu, K;Hattori, N;Sobue, G
对35个受迟发性家族性淀粉样多发性神经病I型（甲状腺素运载蛋白Met30相关家族性淀粉样多发性神经病，FAP TTR Met30）影响的日本家族的临床病理和遗传特征进行了评估，这些家族的兄弟姐妹与日本地方性病灶无关。在这些患者中（50岁或以上），最常见的初始症状是腿部感觉异常。自主神经症状一般较轻，不严重影响日常活动。35个家系中有11个有明显的家族史，其余患者为散发性。症状性携带率低。家族性病例的兄弟姐妹发病年龄晚，男性多见，临床特征与先证者相似。这些迟发性FAP TTR Met30病例的地理分布分散在日本各地。在3例尸检和20例腓肠神经活检标本中，交感神经节和感觉神经节的神经元保存较好，周围神经系统有淀粉样物质沉积，尤以交感神经节、背根神经节和坐骨神经等近端神经干为多。这些异常比在典型的早发性FAP TTR Met30中观察到的那些轻微，如在该疾病的两个日本地方性疫源地中观察到的。虽然有髓纤维中轴突变性突出，导致严重的纤维丢失，但无髓纤维相对保留。我们的晚发型FAP TTR Met30病例显示出与发生在两个日本地方性病灶中的典型早发型FAP TTR Met30不同的特征，需要确定导致这两种形式的FAP TTR Met30之间临床病理差异的因素。
Clinicopathological and genetic features were assessed on 35 Japanese families affected by late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy, FAP TTR Met30) whose siblings were unrelated to endemic Japanese foci, In these patients (50 years or older), the most common initial symptom was paraesthesias in the legs. Autonomic symptoms were generally mild and did not seriously affect daily activities. The male-to-female ratio was extremely high (10.7:1), A family history was evident in only 11 out of 35 families, and other patients were apparently sporadic, The rate of penetrance was very low Symptomatic siblings of familial cases showed a late age of onset, male preponderance and clinical features similar to those of the probands, Asymptomatic carriers, predominantly female, were detected relatively late in life. The geographical distribution of these late-onset, FAP TTR Met30 cases was scattered throughout Japan. In three autopsy cases and 20 sural nerve biopsy specimens, neurons in sympathetic and sensory ganglia were relatively preserved, Amyloid deposition was seen in the peripheral nervous system, particularly in the sympathetic ganglia, dorsal root ganglia and proximal nerve trunks such as sciatic nerve. These abnormalities were milder than those seen in typical early-onset FAP TTR Met30, as observed in two Japanese endemic foci of this disease. While axonal degeneration was prominent in myelinated fibres, resulting in severe fibre loss, unmyelinated fibres were relatively preserved. Our cases of late-onset FAP TTR Met30 showed features distinct from those of typical early-onset FAP TTR Met30 that occurred in the two Japanese endemic foci, Factors responsible for clinicopathological differences between these two forms of FAP TTR Met30 need to be identified.