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.