Planté-Bordeneuve V, Ferreira A, Lalu T, Zaros C, Lacroix C, Adams D, Said G
Centre d'Etude des Neuropathies Amyloïdes Familiales, Service de Neurologie, and Laboratoire Ranvier, Inserm U 788, Hôpital de Bicêtre Assistance Publique Hôpitaux de Paris, Université Paris-Sud, France.
Neurology. 2007 Aug 14;69(7):693-8. doi: 10.1212/01.wnl.0000267338.45673.f4.
Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when associated with autonomic dysfunction.
转甲状腺素蛋白家族性淀粉样多神经病（TTR-FAP）是一种常染色体显性神经病，首发症状出现后10年内会导致致命后果。以非家族性病例就诊的患者诊断延迟，会延误适当的治疗和遗传咨询。我们回顾了300例TTR-FAP患者队列中90例以非家族性病例就诊患者的临床资料。他们中有21名女性和69名男性，发病时的平均年龄为61岁（范围：38至78岁），TTR基因有17种不同突变，包括Val30Met（38例）、Ser77Tyr（16例）、Ile107Val（15例）和Ser77Phe（5例）。初始表现主要包括肢体感觉异常（49例患者）或疼痛（17例患者）。发病时行走困难和无力（5例患者）以及心脏或胃肠道表现（5例患者）较少见。诊断的平均间隔时间为4年（范围1至10年）；18例被误诊为慢性炎症性脱髓鞘性多发性神经病，这是最常见的诊断错误。转诊时，长度依赖性感觉丧失累及下肢的有2例，累及四肢的有20例，累及四肢和前躯干的有77例。60例患者（67%）所有感觉均受累，其他患者以小纤维功能障碍为主。严重自主神经功能障碍影响80例患者（90%），其中52例有体位性低血压，50例有胃肠功能障碍，69例男性中有58例有阳痿，31例有括约肌功能障碍。12例患者需要心脏起搏器。65例患者中有54例经神经活检确诊，30例中有20例经唾液腺活检确诊。神经传导速度减慢、脑脊液蛋白升高、活检结果阴性以及淀粉样沉积物的假免疫标记是诊断错误的主要原因。我们得出结论，对于病因不明的进行性长度依赖性小纤维多发性神经病患者，尤其是伴有自主神经功能障碍的患者，应进行DNA检测，这是TTR-FAP最可靠的检测方法。
