Eye tests reveal possible early signs of Fabry disease in two sisters

Detailed eye exams revealed possible early signs of Fabry disease in two young sisters, according to a new case report. Previously abnormal results from tests measuring retinal and visual pathway function returned to normal ranges 3.5 months after the girls began enzyme replacement therapy (ERT).

Both girls had normal activity of alpha-galactosidase A, an enzyme usually deficient in Fabry disease, but elevated levels of lyso-Gb3, a fatty substance that accumulates in people with the disease. Although other examinations did not clearly establish disease involvement, specialized eye tests revealed subtle changes in both girls.

These included areas of relatively reduced blood vessel-density signals in the retina, the light-sensitive tissue at the back of the eye, and subtle spiral-shaped deposits in the cornea, the clear front surface of the eye. Along with genetic, biochemical, clinical, and family history findings, these eye changes contributed to the decision to start ERT. While structural eye findings remained unchanged at follow-up, previously abnormal visual-function test results were within normal ranges.

Recommended Reading

Nov. 5, 2026 News by Michela Luciano, PhD

US developer gets rights to potential Fabry drug in deal worth up to $475M

Eye exams may help detect early Fabry disease involvement

The researchers suggested that eye examinations could provide valuable information when assessing people with Fabry disease. “Structural and functional ocular changes may provide complementary information regarding disease involvement and longitudinal changes following ERT,” they wrote.

The study, “Structural and functional assessment of ocular findings in two female siblings with fabry disease: potential ophthalmic indicators and changes observed after enzyme replacement therapy — a case report and literature review,” was published in BMC Ophthalmology.

Fabry disease is caused by mutations in the GLA gene that reduce or disrupt the activity of alpha-galactosidase A (alpha-Gal A), an enzyme that helps break down fatty substances such as globotriaosylceramide (Gb3). When the enzyme does not work properly, Gb3 and related substances can build up to harmful levels in the body, causing symptoms affecting multiple organs, including the eyes, skin, kidneys, and heart.

Changes in the eyes may offer a noninvasive way to detect possible disease involvement. Imaging techniques such as optical coherence tomography angiography (OCTA) allow doctors to examine tiny blood vessels in different layers of the retina, potentially revealing subtle changes.

The researchers described two sisters whose detailed eye examinations revealed possible early signs of Fabry-related changes and helped guide the decision to begin treatment.

Two sisters inherited the same Fabry-linked gene mutation

The girls, aged 9.5 and 8 years, were referred to a pediatric clinic in Turkey after their maternal grandfather’s diagnosis of Fabry disease prompted genetic screening of family members. The researchers also reported that their mother carried a disease-causing mutation in the GLA gene, had developed early thickening of the heart muscle and eye abnormalities, and received ERT with Fabrazyme (agalsidase beta).

Genetic testing showed that both girls carried the same GLA mutation as their mother. Doctors then evaluated them for signs of disease involvement and whether treatment was needed.

Both sisters reported occasional abdominal discomfort and brief episodes of pain in their hands and feet, although doctors could not determine whether these symptoms were caused by Fabry. Although their alpha-Gal A activity was normal, their blood lyso-Gb3 levels were elevated, suggesting subclinical disease activity.

Most other test results were normal, including assessments of liver and kidney function, urine, brain MRI, and hearing. Neither girl had characteristic Fabry-related skin lesions called angiokeratomas. The older sister’s heart examinations were also normal. The younger sister was evaluated by a pediatric cardiologist for Wolff-Parkinson-White syndrome, a condition that can cause abnormal heart rhythms. Heart imaging also revealed mild mitral regurgitation, in which the heart’s mitral valve allows some blood to leak backward.

Both sisters had normal vision and eye pressure, but eye examinations revealed cornea verticillata, a characteristic spiral-shaped pattern of deposits in the cornea associated with Fabry disease. These deposits were very mild in the older sister.

Specialized eye tests reveal subtle retinal changes

OCTA revealed localized areas of relatively reduced blood vessel-density signals in superficial and deeper retinal layers, which could indicate early alterations associated with Fabry. However, the cause of these changes could not be determined from the scans alone.

A multidisciplinary team decided to start both sisters on ERT after considering their disease-causing GLA variant, elevated blood levels of lyso-Gb3, characteristic corneal deposits, possible early symptoms, and family history of Fabry. The eye findings provided additional evidence of possible early disease involvement but were not, on their own, the reason for starting treatment.

Researchers also performed noninvasive functional visual electrophysiology tests before treatment and again 3.5 months after ERT began. These tests use flashes of light to measure electrical responses in the retina and the visual pathways leading to the brain. Before starting ERT, both sisters showed abnormal electrical responses on tests of retinal function, including tests assessing retinal nerve cells. The younger sister also showed an abnormal response on a test of the visual pathway connecting the eye to the brain. After 3.5 months of ERT, all previously abnormal test results were within normal ranges.

“These findings suggest that electrophysiological testing may detect subtle functional abnormalities even in the absence of overt structural or systemic involvement, highlighting its potential complementary role in the evaluation of early or subclinical disease involvement,” the researchers wrote.

However, the researchers cautioned that the findings were preliminary. They noted that longer follow-up and studies involving more patients are needed to determine their clinical significance and potential role in monitoring treatment.