Clinical and pathological findings in familial amyloid polyneuropathy caused by a transthyretin E61K mutation
Clinical and pathological findings in familial amyloid polyneuropathy caused by a transthyretin E61K mutation
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DOI：
10.1016/j.jns.2017.08.017
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发表时间：
2017-10-15
影响因子：
4.4
通讯作者：
Sunada, Yoshihide
中科院分区：
文献类型：
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作者：
Murakami, Tatsufumi;Nishimura, Hirotake;Sunada, Yoshihide
家族性淀粉样多发性神经病(FAP)是一种常染色体显性遗传性全身性淀粉样变性，由转甲状腺素(TTR)基因突变引起，早期常表现为感觉显性多发性神经病和自主神经病变。尽管已经提出了几种机制，包括机械压迫、血管闭塞、TTR毒性和雪旺细胞功能障碍，但其发病机制尚不清楚。我们描述了一例由TTRE61K突变引起的迟发性FAP患者。发病7年后，在腓肠神经的神经内膜或神经周围未发现淀粉样沉积，但在腓肠神经中观察到明显的神经纤维丢失。在腓骨短肌、唾液腺和心脏组织中证实了TTR来源的淀粉样沉积。DNA分析显示TTR区存在杂合性突变。这些发现表明，周围神经系统的近端可能受到TTR聚集体或淀粉样纤维的强烈影响，而周围神经远端的血-神经屏障最初在该患者中被保留。本病例提示神经以外的几个活检部位对诊断轻度或晚发型FAP的TTR淀粉样变性可能是有帮助和必要的。
Familial amyloid polyneuropathy (FAP) is an autosomal dominant hereditary systemic amyloidosis caused by mutation of the transthyretin (TTR) gene, and usually shows sensory-dominant polyneuropathy and autonomic neuropathy at the initial stage. The pathogenesis of this neuropathy remains unknown, although several mechanisms, including mechanical compression, vessel occlusion, TTR toxicity and Schwann cell dysfunction have been proposed. We describe a patient with late-onset FAP caused by a TTR E61K mutation. Amyloid deposits were not detected in the endoneurium or perineurium of the sural nerve 7 years after the onset of the disease, but a marked loss of nerve fibers was observed in the sural nerve. TTR-derived amyloid deposits were confirmed in the peroneus brevis muscle, salivary gland and heart tissue. DNA analysis revealed a heterozygous mutation in TTR. These findings suggest that proximal parts of the peripheral nervous system might be strongly affected by TTR aggregates or amyloid fibrils, and that the blood-nerve barrier in distal parts of peripheral nerves are initially preserved in this patient. This case indicates that several biopsy sites other than nerves may be helpful and necessary for the diagnosis of TTR amyloidosis in mild or late-onset FAP.