Malik Muhammad Reebal, Dalia Tarun, Shah Zubair
Central Park Medical College, Lahore, Pakistan.
University of Kansas Medical Center, Kansas City, USA.
J Med Case Rep. 2025 Aug 4;19(1):384. doi: 10.1186/s13256-025-05308-w.
Transthyretin is a protein produced by the liver, and when normal, it carries out the role of transporting thyroid hormone and vitamin A in the body. Mutations in the gene that codes for this protein can cause it to misfold. A misfolded protein can not carry out its functions and can also build up in different organs leading to a group of diseases known as amyloidosis. Depending upon the site in which this protein accumulates, a large variety of symptoms can be seen. If the protein deposits in the heart, it can lead to heart failure and associated symptoms and is known as cardiac amyloidosis. If in the nerves, it can lead to neuropathy and tingling and numbness and so on. Due to the various symptom's transthyretin amyloidosis can present with, it is difficult to keep it on the differential and diagnose the disease, as suspicions for it should be high. We would like to use this case report to help raise awareness about hereditary transthyretin amyloidosis.
A 66-year-old Mexican male patient with a family history significant for hereditary amyloidosis presented with intermittent chest pain, shortness of breath, and neurological symptoms. An echocardiogram done at an outside hospital showed an ejection fraction of 55-60% with grade 2 diastolic dysfunction. A technetium pyrophosphate scan was used to make the diagnosis of transthyretin amyloidosis, and genetic testing showed that the patient was heterozygous for p.G67A (also known as c.2000G > C) pathogenic mutation in the transthyretin (TTR) gene. Due to these findings the patient was started on tafamidis free acid 61 mg daily and vutrisiran (Amvuttra) injections. He was also given vitamin A supplementation to prevent vutrisiran-associated vitamin A deficiency, which is a known side effect.
A high index of suspicion is required for diagnosing transthyretin amyloidosis. This case will help raise awareness among physicians regarding the presence of the G67A mutation in Mexican patients and its management.
转甲状腺素蛋白是一种由肝脏产生的蛋白质，在正常情况下，它在体内发挥运输甲状腺激素和维生素A的作用。编码这种蛋白质的基因突变会导致其错误折叠。错误折叠的蛋白质无法发挥其功能，还会在不同器官中积聚，导致一组称为淀粉样变性的疾病。根据这种蛋白质积聚的部位，可以观察到各种各样的症状。如果蛋白质沉积在心脏，会导致心力衰竭及相关症状，称为心脏淀粉样变性。如果沉积在神经中，会导致神经病变、刺痛和麻木等。由于转甲状腺素蛋白淀粉样变性可能出现的各种症状，很难将其纳入鉴别诊断并诊断该疾病，因此对此病的怀疑度应很高。我们希望通过本病例报告来提高对遗传性转甲状腺素蛋白淀粉样变性的认识。
一名66岁的墨西哥男性患者，有显著的遗传性淀粉样变性家族史，出现间歇性胸痛、呼吸急促和神经症状。在外院进行的超声心动图显示射血分数为55 - 60%，伴有2级舒张功能障碍。使用焦磷酸锝扫描诊断为转甲状腺素蛋白淀粉样变性，基因检测显示患者在转甲状腺素蛋白（TTR）基因中存在p.G67A（也称为c.2000G＞C）致病突变的杂合子。基于这些发现，患者开始每日服用61毫克的他氟米特游离酸并注射vutrisiran（Amvuttra）。还给他补充了维生素A以预防vutrisiran相关的维生素A缺乏，这是一种已知的副作用。
诊断转甲状腺素蛋白淀粉样变性需要高度的怀疑指数。本病例将有助于提高医生对墨西哥患者中G67A突变的存在及其管理的认识。
