Abulikemu Kebinuer, Hong Lei, Zhong Qinghua
Department of Cardiovascular Medicine, Shenzhen Longgang Central Hospital, Shenzhen, Guangdong, China.
Front Cardiovasc Med. 2025 Sep 2;12:1625485. doi: 10.3389/fcvm.2025.1625485. eCollection 2025.
Familial transthyretin amyloidosis (ATTR) is a rare hereditary disorder marked by abnormal protein fibril deposits that impair multiple organ functions. Although over 130 mutations have been identified, the p.Ser43Asn variant, which has been associated with amyloidosis involving thyroxine-binding globulin (TBG), is scarcely reported in the literature, especially within the Chinese population.
We report a case of a 50-year-old male presenting with recurrent episodes of amaurosis fugax. The patient had a family history of cardiac disease. Auxiliary examinations revealed myocardial hypertrophy, and the electrocardiogram indicated conduction delays and abnormal QRS complexes. Nuclear imaging suggested cardiac amyloidosis, and cardiac MRI indicated non-ischemic cardiomyopathy. Genetic testing identified a c.128G > A (p.Ser43Asn) mutation, and pathological examination confirmed ATTR amyloidosis. Both pathological findings and mass spectrometry analysis supported this diagnosis.
The p.Ser43Asn variant likely impacts TTR protein dimerization and stability, leading to protein misfolding and amyloid fibril deposition in tissues. Early diagnosis is crucial due to the significant heterogeneity of this condition. Our findings emphasize the importance of increased diagnostic awareness, multidisciplinary collaboration, and regional genetic screening. Comparisons with similar cases reported in the literature highlight the shared clinical presentations and diagnostic challenges.
This case adds valuable insight into the clinical manifestations and diagnostic challenges of ATTR amyloidosis with the p.Ser43Asn mutation, particularly in the Chinese population. Future research should aim to develop effective treatment strategies and explore the genetic and environmental factors influencing the phenotypic variability of this rare disorder.
家族性转甲状腺素蛋白淀粉样变性（ATTR）是一种罕见的遗传性疾病，其特征是异常蛋白纤维沉积，损害多个器官功能。尽管已鉴定出130多种突变，但与涉及甲状腺素结合球蛋白（TBG）的淀粉样变性相关的p.Ser43Asn变体在文献中鲜有报道，尤其是在中国人群中。
我们报告一例50岁男性，反复出现一过性黑矇发作。该患者有心脏病家族史。辅助检查显示心肌肥厚，心电图提示传导延迟和QRS波群异常。核成像提示心脏淀粉样变性，心脏磁共振成像提示非缺血性心肌病。基因检测发现c.128G＞A（p.Ser43Asn）突变，病理检查确诊为ATTR淀粉样变性。病理结果和质谱分析均支持这一诊断。
p.Ser43Asn变体可能影响转甲状腺素蛋白（TTR）的二聚化和稳定性，导致蛋白质错误折叠和淀粉样纤维在组织中沉积。由于该病具有显著的异质性，早期诊断至关重要。我们的研究结果强调了提高诊断意识、多学科协作和区域基因筛查的重要性。与文献中报道的类似病例进行比较，突出了共同的临床表现和诊断挑战。
本病例为p.Ser43Asn突变的ATTR淀粉样变性的临床表现和诊断挑战提供了有价值的见解，尤其是在中国人群中。未来的研究应致力于开发有效的治疗策略，并探索影响这种罕见疾病表型变异的遗传和环境因素。
