Mild to moderate impaired brain blood flow common in Fabry disease
Researchers: NfL blood levels might be easy test to do for brain involvement

Mild to moderate cerebrovascular disease, which occurs when blood flow in the brain is impaired, is a characteristic brain signature in adults with Fabry disease, according to a new study.
Nearly half of those examined showed signs of white matter damage, for which impaired kidney function was the sole predictive factor. Also, more than two-thirds had signs of cognitive impairment.
Blood levels of neurofilament light chain (NfL), a biomarker for nerve damage, may represent a potentially sensitive and easy test to perform for brain involvement in Fabry, according to the study’s researchers. The study, “Prevalence and Clinical Correlates of Cerebrovascular Alterations in Fabry Disease: A Cross-Sectional Study,” was published in Brain Sciences.
Fabry is a rare inherited disorder characterized by the toxic buildup in cells of a fatty substance known as globotriaosylceramide, or Gb3, which disrupts organ function, especially the kidneys and heart. Cerebrovascular disease is another manifestation of Fabry, where blood flow in the brain is slowed or stopped, increasing the risk of stroke, damage to the brain’s white matter, and cognitive decline.
Cerebrovascular disease and Fabry
Because so few studies have described the impact of Fabry on the brain, a research team in Italy assessed the cerebrovascular and cognitive manifestations of Fabry in a study group of 40 adults with the disease, of whom 23 (57.5%) were women. Most (60%) were diagnosed with classic Fabry, while the remaining had late-onset Fabry disease (40%). Nearly all (80%) were undergoing Fabry-specific treatment at the time of the assessment.
About 1 in 4 patients (22.5%) had had major cardiac events, including irregular heartbeats, heart attack, or congestive heart failure. About half (55%) had high blood pressure, cardiac hypertrophy (45%), a thickening of the heart muscle, or kidney impairment (50%).
Four (10%) patients had had a stroke, one of whom also had multiple transient ischemic attacks, a temporary blockage of blood flow to the brain. All the strokes occurred in late-onset Fabry patients.
Of the 32 patients who received an MRI scan, 13 (40.6%) showed signs of white matter damage. Seven (21.9%) had mild damage, three (9.4%) had moderate damage, and three (9.4%) had severe white matter damage. No MRI differences were noted between those treated or untreated, or men and women.
Among the 39 patients who underwent a battery of cognitive assessments, more than two-thirds (69.2%) showed impairment on at least one test, with no differences between men and women. Most prominently, roughly 1 in 3 patients (28% to 33%) had problems copying and recalling Rey’s complex figure, an assessment to evaluate visual memory and visuospatial skills.
Blood levels of NfL were higher in Fabry patients than in healthy people matched for age and sex (median, 11.5 vs. 7.12 picomoles/mL), although the difference wasn’t statistically significant. Mean NfL levels didn’t differ according to sex or clinical presentation (classic vs. late-onset).
In a statistical analysis, impaired kidney function, as assessed by the estimated glomerular filtration rate (eGFR), was the sole significant predictor of white matter damage. Among individual comparisons, high NfL levels significantly correlated with worse kidney function via eGFR and cognitive impairment, as indicated by the Mini-Mental State Examination.
“Our study confirms that mild to moderate [cerebrovascular disease] is a characteristic brain ‘signature’ in [Fabry] patients, regardless of [sex] and phenotype, but coherent with overall disease severity,” the authors wrote. “NfL might represent a potential sensitive and easy to perform biomarker of [brain and spinal cord] damage in [Fabry], either to monitor disease progression and response to treatments.”