Cerebral Small Vessel Disease and Stroke Risk in Fabry Patients


A small study found a correlation between age and small vessel disease risk that suggest the importance of regular brain MRI monitoring in patients with Fabry.

Fabry disease (FD) is a rare inherited lysosomal storage disorder that affects the central nervous system, but data on cerebrovascular neuroimaging in FD patients are limited. A small study published in Molecular Genetics and Metabolism Reports evaluated a cohort of FD patients to assess the prevalence of brain ischemia and cerebral small vessel disease (SVD) in this population.

FD is caused by mutations in the GLA gene, which encodes for the enzyme alpha-galactosidase A. GLA deficiency causes globotriaosylceramide (GL-3) to accumulate within lysosomes and affects a multitude of cell types. The heart and kidneys are most commonly affected, and cerebrovascular complications are also often present. The study authors noted that one review found a reported stroke incidence of 24% to 48% in FD patients, with the majority of strokes being ischemic. FD patients are at a 12-fold increased risk of transient ischemic attack and stroke.

SVD is a common cerebrovascular occurrence in aging adults, but a deeper knowledge of the prevalence and severity of SVD in FD patients could potentially help identify those at higher risk of stroke. The signs of SVD in MRI scans are small deep infarcts, cerebral microbleeds, white matter hyperintensities (WMH), and enlarged perivascular spaces. Each detectable MRI feature adds a point to the scale that quantifies cerebral SVD on a standardized and objective measurement.

In the current study, 21 patients with FD being seen twice per year at University of California Irvine Medical Center underwent brain MRIs. An SVD score rated 3 variables—lacunes, deep WMH, and microbleeds—to assess SVD presence and severity. The mean patient age was 50 years (range 32-81) at the time of MRI, and the majority of patients were female (62%).

In the study cohort, 43% of patients showed signs of cerebral SVD. This was 3 times the number of patients who had a previous stroke. Age was correlated with SVD score, indicating increased stroke risk, but FD patients tended to have signs of SVD earlier than the general population.

“While previous studies have shown that SVD in the form of white matter lesions are predominant in the general population after the age of 60 years, we found that in our FD cohort the occurrence was evident one decade earlier at age 50,” the authors wrote.

In addition to the correlation between age and SVD, 78% of patients who had a total SVD score greater than 0 showed more than just WMH in their MRIs. This aligns with previous findings and is unique to FD patients compared with the general population, according to the study authors.

“Our findings suggest that using an SVD score to characterize extent of SVD in FD patients might help better predict those at increased risk for developing a stroke,” the authors wrote.

Overall, 76% of patients were being treated with enzyme replacement therapy (ERT) at the time of the study. While ERT has been shown to improve disease in the heart and kidneys, its effects on cerebrovascular risk factors over time. The authors suggest it may be beneficial to utilize SVD scores to track this progression, since brain MRI scans are recommended every 3 years for routine FD screening.

Despite the small sample size in the study, authors conclude that FD patients may have increased SVD scores earlier than the general population, starting at 50 to 60 years of age. More research is necessary to confirm the prevalence and severity of SVD in this patient population, but the study’s findings support the importance of regular MRIs in FD patients.


Tapia D, Floriolli D, Han E, et al. Prevalence of cerebral small vessel disease in a Fabry disease cohort. Mol Genet Metab Rep. Published online October 21, 2021. doi:10.1016/j.ymgmr.2021.100815

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