Suspect early, diagnose quickly for Stargardt disease¹

Stargardt disease type 1, or STGD1, is a progressive inherited retinal disease. This autosomal recessive condition is caused by mutations in the ABCA4 gene, leading to uncorrectable central vision loss.

The most common early symptoms include central vision that is blurry, distorted, or has dark areas. Many patients begin to exhibit symptoms as early as childhood or adolescence.

Because Stargardt disease diagnosis often takes years, many patients experience irreversible vision loss before receiving a confirmed genetic diagnosis.

To understand how Stargardt disease progresses, let’s look at the visual cycle.

Vitamin A derivatives are the chemical backbone of this process. Vitamin A is delivered to the retinal pigment epithelium—or RPE—cells in the retina via the bloodstream, bound in a complex by retinol binding protein 4.

RPE cells process vitamin A into an activated form that is then shuttled to the photoreceptor cell, where it is used to sense light. When photoreceptors absorb light, they initiate the electrical cascade that the brain interprets as vision.

Vitamin A is then inactivated and converted into a reactive byproduct. Healthy vision requires continuous recycling of this byproduct. ABCA4 is a critical transporter protein for shuttling these byproducts across photoreceptor membranes to return them to the RPE for processing.

In Stargardt disease, ABCA4 dysfunction disrupts this recycling process. The visual cycle byproduct builds up in photoreceptors, promoting formation of toxic molecules called bisretinoids.

As RPE cells continuously process photoreceptor waste, these bisretinoids cannot be degraded, which drives accumulation of a substance called lipofuscin. Bisretinoids compromise metabolic processes in the RPE, leading to increased lipofuscin formation, impaired RPE cell function, and RPE cell death.

Because photoreceptors rely on RPE cells for metabolic support, RPE degradation and death inevitably results in degradation and loss of corresponding photoreceptors. This appears as atrophic lesions in the retina.

Clinically, this progressive atrophy and lesion growth in the retinal tissue translates to the central vision loss characteristic of Stargardt disease. In patients with a suspected clinical diagnosis of Stargardt disease, genetic testing that includes the ABCA4 gene can be valuable to confirm the diagnosis and optimize management.

Although there are currently no approved treatments for Stargardt disease, new interventions are an area of active research and development.