Kamimoto Hiroyuki, Tomioka Daisuke, Hanato Kai, Takagi Shunsuke, Uemura Yuki, Dochi Kenichi, Sakai Hiroshi, Ueno Yoshiki
Department of Cardiology, Shiga Medical University, Shiga, Japan.
Department of Cardiology, Nagahama Red Cross Hospital, Shiga, Japan.
J Cardiol Cases. 2024 Jan 28;29(5):201-204. doi: 10.1016/j.jccase.2024.01.002. eCollection 2024 May.
Hereditary transthyretin amyloidosis is autosomal dominant and results from mutations in the transthyretin gene. The Val30Met variant is the most common genetic mutation, although mutations vary within populations. More than 150 mutations in transthyretin have been reported; however, the Leu111Glu (p. Leu131Glu) mutation has been reported to date. We report the case of a 32-year-old Japanese male with a history of cerebral hemorrhage and hydrocephalus at age 27 years. The patient was referred to our department after his sibling had been diagnosed with hereditary transthyretin amyloidosis. Twelve-lead electrocardiography exhibited poor R progression, and transthoracic echocardiography showed normal findings. Tc-labelled pyrophosphate scintigraphy showed high accumulation in the heart. Histological tests using a right ventricular endomyocardial biopsy showed amyloid deposits and immunostaining only for transthyretin. Genetic analysis confirmed a novel missense variant, Leu111Glu, on the transthyretin gene. We diagnosed the patient with hereditary transthyretin amyloidosis, and the patient received genetic counseling. Patients with hereditary transthyretin amyloidosis carrying the Leu111Gln variant may present as a patient with a hydrocephalus-dominant phenotype. To the best of our knowledge, this is the first case report of the transthyretin Leu111Glu variant.
Hereditary transthyretin amyloidosis with the Leu111Gln variant has not been previously reported in Japan. While cardiac involvement progresses without overt abnormal findings on electrocardiogram and echocardiogram, Tc-labelled pyrophosphate scintigraphy can be a useful tool for the early diagnosis of hereditary transthyretin amyloidosis. This mutation may result in a predominantly hydrocephalus phenotype, and organ damage is expected to progress rapidly. Therefore, early diagnosis and appropriate treatment are necessary.
遗传性转甲状腺素蛋白淀粉样变性是常染色体显性遗传，由转甲状腺素蛋白基因突变引起。Val30Met变异是最常见的基因突变，尽管不同人群中的突变有所不同。已报道转甲状腺素蛋白有超过150种突变；然而，Leu111Glu（p.Leu131Glu）突变至今尚未见报道。我们报告一例32岁日本男性病例，该患者27岁时有脑出血和脑积水病史。其同胞被诊断为遗传性转甲状腺素蛋白淀粉样变性后，该患者转诊至我科。十二导联心电图显示R波递增不良，经胸超声心动图检查结果正常。锝标记焦磷酸闪烁扫描显示心脏有高度聚集。右心室心内膜活检的组织学检查显示有淀粉样沉积物，且仅对转甲状腺素蛋白进行免疫染色呈阳性。基因分析证实转甲状腺素蛋白基因上有一个新的错义变异Leu111Glu。我们诊断该患者患有遗传性转甲状腺素蛋白淀粉样变性，并为患者提供了遗传咨询。携带Leu111Gln变异的遗传性转甲状腺素蛋白淀粉样变性患者可能表现为以脑积水为主的表型。据我们所知，这是转甲状腺素蛋白Leu111Glu变异的首例病例报告。
日本此前尚未报道过携带Leu111Gln变异的遗传性转甲状腺素蛋白淀粉样变性。虽然心脏受累在心电图和超声心动图无明显异常表现的情况下进展，但锝标记焦磷酸闪烁扫描可能是遗传性转甲状腺素蛋白淀粉样变性早期诊断的有用工具。这种突变可能导致以脑积水为主的表型，且器官损害预计会迅速进展。因此，早期诊断和适当治疗是必要的。
