Eriksson Magdalena, Büttner Janine, Todorov Theodor, Yumlu Saniye, Schönland Stefan, Hegenbart Ute, Kristen Arnt V, Dengler Thomas, Lohse Peter, Helmke Burkhard, Schmidt Hartmut, Röcken Christoph
Department of Pathology, Medical Clinic of Gastroenterology, Hepatology, and Endocrinology, Charité University Hospital, Berlin, Germany.
Am J Surg Pathol. 2009 Jan;33(1):58-65. doi: 10.1097/PAS.0b013e3181788566.
Transthyretin-derived amyloidosis (ATTR) amyloidosis is the third most prevalent amyloid type in surgical pathology and may occur as a hereditary disease with germline mutations in the TTR gene or as senile systemic amyloidosis (SSA) without mutations. Distinction between hereditary ATTR amyloidosis and SSA is of central importance, as the former necessitates genetic counseling and can be treated by liver transplantation. However, little is known about the prevalence of hereditary ATTR amyloidosis in surgical pathology specimens. We have examined the distribution of hereditary ATTR amyloidosis and SSA in a consecutive series of surgical pathology specimens with histologically and immunohistochemically confirmed ATTR amyloid. Thirty-three consecutive patients were retrieved from the Amyloid Registry of the Charité University Hospital. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue or patient blood and examined by DNA sequencing. ATTR amyloid was found in the gastrointestinal tract, endomyocardium, peripheral nerve, carpal tunnel ligament, synovia, breast, and testicle. Amyloid fibrils were present as interstitial and vascular deposits, as evidenced by Congo red staining. TTR gene mutations were detected in 12 of 30 patients, with p.Val30Met being the most prevalent (5 patients). Furthermore, 2 novel mutations (p.Asp39Val and p.Glu54Asp) were found. In patients carrying a mutation, ATTR amyloid was found in the gastrointestinal tract, myocardium, nerve, and testicles. To conclude, the hereditary form of ATTR amyloid seems to be more common in elderly patients than previously thought. It is, therefore, important to genetically test every patient when diagnosing ATTR amyloidosis.
转甲状腺素蛋白衍生的淀粉样变性（ATTR）淀粉样变性是外科病理学中第三常见的淀粉样变类型，可作为一种伴有转甲状腺素蛋白（TTR）基因种系突变的遗传性疾病出现，也可作为无突变的老年系统性淀粉样变性（SSA）出现。区分遗传性ATTR淀粉样变性和SSA至关重要，因为前者需要进行遗传咨询，并且可以通过肝移植进行治疗。然而，关于遗传性ATTR淀粉样变性在外科病理标本中的患病率知之甚少。我们在一系列经组织学和免疫组织化学证实为ATTR淀粉样变性的外科病理标本中，研究了遗传性ATTR淀粉样变性和SSA的分布情况。从夏里特大学医院的淀粉样变性登记处检索了33例连续病例。从福尔马林固定石蜡包埋组织或患者血液中提取基因组DNA，并通过DNA测序进行检测。ATTR淀粉样变性见于胃肠道、心内膜、周围神经、腕管韧带、滑膜、乳腺和睾丸。刚果红染色显示淀粉样纤维以间质和血管沉积物的形式存在。在30例患者中有12例检测到TTR基因突变，其中p.Val30Met最为常见（5例）。此外，还发现了2种新的突变（p.Asp39Val和p.Glu54Asp）。在携带突变的患者中，ATTR淀粉样变性见于胃肠道、心肌、神经和睾丸。总之，ATTR淀粉样变性的遗传形式在老年患者中似乎比以前认为的更为常见。因此，在诊断ATTR淀粉样变性时，对每位患者进行基因检测很重要。
