Csillik Anita, Pozsonyi Zoltán, Soós Krisztina, Balogh István, Bodó Imre, Arányi Zsuzsanna
MTA-SE NAP B Peripheriás Idegrendszeri Kutatócsoport, Semmelweis Egyetem, Neurológiai Klinika, Budapest.
Semmelweis Egyetem, III. Sz. Belgyógyászati Klinika, Budapest.
Ideggyogy Sz. 2016 Jul 30;69(7-8):245-253. doi: 10.18071/isz.69.0245.
Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal dominant progressive systemic disesase of adults caused by endoneural amyloid deposition due to point mutations of the transthyretin gene. It is the most severe form among hereditary polyneuropathies, being fatal within 10 years if left untreated. The disease is underdiagnosed, the late onset forms (above the age of 50) being probably more widespread than previously thought. Early diagnosis is essential as the early introduction of causal therapy (tafamidis) slows progression and prolongs survival. Patients - We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non-Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all characterized by late-onset, progressive, length-dependent, axonal, sensorimotor polyneuropathy and the simultaneous presentation of severe restrictive cardiomyopathy. In all three cases, clinical and electrophysiological signs of myopathy were also present, suggesting the involvement of skeletal muscles as well. In two cases, high resolution ultrasound of the peripheral nerves was also performed, which showed segmental structural alterations (change or loss of fascicular structure) and some increase of echogenicity of the interfascicular epineurium, without substantial enlargement of the nerves. Conclusion - In Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial amyloid polyneuropathy are encountered, as in our cases. As opposed to the Val30Met forms, these mutations are characterized by late onset and simultaneous presentation of severe cardiomyopathy. Our report highlights the importance of considering transthyretin familial amyloid polyneuropathy in the differential diagnosis of late-onset, progressive, axonal polyneuropathies of unknown etiology, particularly if associated with cardiac disease.
引言——转甲状腺素蛋白家族性淀粉样多神经病是一种罕见的常染色体显性遗传性成人进行性全身性疾病，由转甲状腺素蛋白基因的点突变导致神经内膜淀粉样沉积引起。它是遗传性多神经病中最严重的一种形式，若不治疗，10年内会致命。该疾病诊断不足，晚发型（50岁以上）可能比之前认为的更为普遍。早期诊断至关重要，因为早期引入病因治疗（他氟米特）可减缓病情进展并延长生存期。
患者——我们在此报告3例非相关的匈牙利转甲状腺素蛋白家族性淀粉样多神经病病例，均为非Val30Met突变（2例为His88Arg，1例为Phe33Leu）。它们均具有晚发、进行性、长度依赖性、轴索性、感觉运动性多神经病的特征，同时伴有严重的限制性心肌病。所有3例患者还均有肌病的临床和电生理体征，提示骨骼肌也受累。2例患者还进行了周围神经高分辨率超声检查，结果显示节段性结构改变（束状结构改变或消失）以及束间神经内膜回声略有增强，神经无明显增粗。
结论——在匈牙利，如我们的病例所示，主要遇到的是转甲状腺素蛋白家族性淀粉样多神经病罕见的非Val30Met突变形式。与Val30Met形式不同，这些突变的特点是发病晚且同时伴有严重心肌病。我们的报告强调了在病因不明的晚发、进行性、轴索性多神经病的鉴别诊断中，尤其是伴有心脏疾病时，考虑转甲状腺素蛋白家族性淀粉样多神经病的重要性。
