一种罕见的异常侵袭性遗传性甲状腺转蛋白淀粉样变

Q4 Medicine

JACC. Case reports Pub Date : 2025-10-01 DOI:10.1016/j.jaccas.2025.105309

Jingwen Zhang MD , Lori R. Roth PA-C , Isabel Wees MD , Lauren Phillips MD , Rose Pedretti PhD , Pauline Nguyen MS , Lorena Saelices PhD , Justin L. Grodin MD, MPH

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引用次数: 0

摘要

与野生型ATTR相比，遗传性甲状腺转蛋白淀粉样变性（ATTRv）更典型地与早期发病和神经系统症状相关，尽管非常早期、非常有症状的疾病表现很少见。病例总结：一名21岁男性，在胃肠道活检确诊为ATTR后，接受了心脏评估。淀粉样变和过早死亡的家族史是显著的。检查显示神经功能缺损，无临床心衰，超声心动图显示左心室同心重构。TTR基因测序鉴定出一种罕见的致病变异p.Phe84Ser。磁共振成像显示脑和脊柱弥漫性轻脑膜增强。开始使用伏曲西兰和他法米底斯治疗。p.Phe84Ser变异与中枢神经系统和胃肠道受累密切相关。这个病人有一个早期的表型表现为脑膜淀粉样变，这是非常罕见的。了解与该ATTRv基因型相关的表型，以及患者的家族史，指导有针对性和及时的评估和治疗。

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A Rare Unusually Aggressive Form of Hereditary Transthyretin Amyloidosis

Background

Hereditary transthyretin amyloidosis (ATTRv) is more typically associated with earlier onset and neurological symptoms compared with wild-type ATTR, although a very early, very symptomatic disease presentation is rare.

Case Summary

A 21-year-old male with gastrointestinal distress and neuropathy underwent cardiac evaluation after gastrointestinal biopsies identified ATTR. Family history was notable for amyloidosis and premature deaths. Examination showed neurological deficits without clinical heart failure, and echocardiogram showed concentric left ventricular remodeling. TTR gene sequencing identified a rare pathogenic variant, p.Phe84Ser. Magnetic resonance imaging demonstrated diffuse leptomeningeal enhancement of the brain and spine. Treatment with vutrisiran and tafamidis was initiated.

Discussion

The p.Phe84Ser variant is strongly associated with central nervous system and gastrointestinal involvement. This patient had an early phenotypic presentation with leptomeningeal amyloidosis, which is exceedingly rare.

Take-Home Message

Understanding the phenotype associated with this ATTRv genotype, along with the patient's family history, guided targeted and timely evaluation and treatment.

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