Gender Matters for White Matter Lesion Development in Fabry Disease Patients

New research from the University of Amsterdam, the Netherlands, suggests that a significant group of Fabry disease patients have substantial white matter lesions on their brains. Additionally, it appears that male patients develop white matter lesions earlier than their female counterparts.

In a recent meta-analysis, investigators set out to assess the prevalence, severity, location, and course of white matter lesions in Fabry disease patients; they also wanted to understand the existing evidence on the relationship between the lesions, Fabry disease characteristics, and the clinical parameters.

The investigators scoured the Pubmed, EMBASE, and CINAHL databases from their inception to February of 2018 to identify articles on Fabry disease and white matter lesions examined with MRI testing. In total, they discovered 904 studies, 46 of which were included in the final analysis.

“In the general population, white matter lesions have been strongly linked to high blood pressure, smoking, and other risk factors,” study author Simon Korver told Rare Disease Report^®. “The absence of such a relationship in the Fabry patients implies that the cause of white matter lesions in Fabry disease differs from the general population.”

White matter lesions were found in nearly half of the Fabry disease patients (46%) and increased with age, the investigators reported. They also found that 16.4% of the total patients showed substantial confluent white matter lesions. While men and women showed comparable prevalence and severity of white matter lesions, it seemed that men were significantly younger at the time of white matter lesion assessment.

One-quarter of the patients had white matter lesion progression after an average of 38 months of follow up, they added; this occurred in both men and women—regardless of the use of enzyme replacement therapy—however, this happened at an earlier age in male patients.

Having a stroke also appeared to be related to white matter lesions, the investigators said. Other cerebrovascular risk factors did not, nor did cardiac or renal function.

“The clinical consequences of white matter lesions have barely been addressed in previous studies in Fabry disease,” Dr. Korver said. “There is some evidence that more white matter lesions are associated with a higher risk of stroke or cognitive decline. However, this relation has not been conclusively established and deserves more attention since it is highly relevant for the patients.”

White matter lesions are commonly found in the elderly among the general population, without Fabry disease, the investigators pointed out. However, when found in such prevalence and severity in Fabry disease patients, it can correspond to healthy individuals between 1 and 3 decades older.

“Physicians should be critical about starting enzyme replacement therapy in patients who have white matter lesions as a single clinical feature of Fabry disease since evidence on prevention of white matter lesion progression using this treatment is lacking,” Dr. Korver said when asked what physicians should take away from his findings. “Moreover, patients with extensive white matter lesions might be at higher risk for cognitive decline and stroke and this should, therefore, be monitored.”

The paper, titled “Development and clinical consequences of white matter lesions in Fabry disease: A systematic review,” was published in Molecular Genetics and Metabolism.