探讨累及多系统的迟发型法布里病(FD)的临床特征与诊断策略。

回顾性分析2024年8月27日济宁医学院附属医院神经内科收治的1例迟发型FD患者的临床资料及诊治过程，总结其漏诊启示及诊断学特征。

患者男性，60岁，因左手知觉差、左下肢无力14 h就诊。既往有腔隙性脑梗死病史14年，伴耳鸣、蛋白尿14年，左心室肥厚12年。本次入院颅脑MRI示右枕顶叶急性期脑梗死；心脏MRI示左室壁不均匀性增厚(最厚19 mm)，余节段初始T₁值弥漫性减低；左室侧壁见明显钆延迟强化伴局部T₁、T₂值增高。基因检测示GLA：c.671A>G(p.Asn224Ser)半合子错义突变；α-半乳糖苷酶A活性[0.97 μmol/(L·h)]降低；生物标记物脱乙酰基-三己糖酰基鞘酯醇(Lyso-Gb3)水平明显升高(48.41 μg/L)，尿微量白蛋白1 170.0 mg/L，眼裂隙灯检查见双眼角膜涡状混浊，确诊为FD。患者自首发症状至确诊历时14年，漏诊原因在于多系统受累表现未被溯源整合。

对于不明原因脑卒中、心肌肥厚合并蛋白尿等多系统受累者，应警惕FD可能，需及时行酶学与基因检测。

To explore the clinical features and diagnostic strategies of delayed-onset Fabry disease (FD) involving multiple systems.

A retrospective analysis was conducted on the clinical data and treatment process of a patient with delayed-onset FD admitted to the Department of Neurology, the Affiliated Hospital of Jining Medical University on August 27, 2024. The lessons from the diagnostic delay and key diagnostic features were summarized.

A 60-year-old male presented with a 14-hour history of hypoesthesia in the left hand and weakness in the left lower limb. The patient had a history of lacunar cerebral infarction (14 years), tinnitus and proteinuria (14 years), and left ventricular hypertrophy (12 years). On admission, cranial MRI revealed an acute cerebral infarction in the right parieto-occipital lobe. Cardiac MRI revealed non-uniform left ventricular wall thickening (maximal wall thickness of 19 mm), diffuse reduction of native T₁ values in the remaining myocardial segments, and marked late gadolinium enhancement (LGE) with localized elevated T₁ and T₂ values in the left ventricular lateral wall. Genetic testing identified a hemizygous missense variation in the GLA gene: c. 671A>G (p.Asn224Ser). Furthermore, enzymatic activity of α-galactosidase A [0.97 μmol/(L·h)] was decreased, and the biomarker Lyso-Gb3 (48.41 μg/L) was markedly elevated; urinary microalbumin was level 1 170.0 mg/L, and slit-lamp examination revealed bilateral cornea verticillata, confirming the diagnosis of FD. Notably, the patient experienced a diagnostic delay of 14 years from the onset of initial symptoms to definitive diagnosis. The primary reason for this missed diagnosis was the failure to trace and integrate the multisystem manifestations into a unified etiology.

FD should be considered in the differential diagnosis for patients with cryptogenic stroke, left ventricular hypertrophy, and proteinuria. Prompt enzymatic assays and genetic analysis are crucial for early confirmation.