Cathepsin A-related arteriopathy-strokes-leukoencephalopathy (CARASAL): A Patient Guide

Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is an ultra-rare genetic disorder that affects the small blood vessels deep within the brain. It belongs to a group of conditions known as hereditary cerebral small vessel diseases, which are caused by specific genetic mutations that damage the brain’s “plumbing” over time ^[1]. In CARASAL, a mutation in the CTSA gene disrupts the normal function of a protein called cathepsin A, which is responsible for maintaining the health of blood vessels and regulating other vital proteins in the brain ^[2].

One of the most striking characteristics of CARASAL is how it appears on medical imaging compared to how a patient feels. Doctors often observe a “clinicoradiological dissociation,” where a brain MRI shows extensive, widespread damage to the white matter (the brain’s wiring) even when the patient has only very mild or subtle symptoms ^[2]. This disproportionate white matter disease is thought to be driven by an accumulation of a protein called endothelin-1, which may prevent the brain from properly repairing its insulation even before significant blood vessel blockages occur ^[3][2].

Living with CARASAL requires careful medical navigation because the condition creates a dual risk for two different types of strokes. The damaged small vessels can become blocked, leading to ischemic strokes, or they can become fragile and burst, causing intracerebral hemorrhages (brain bleeds) ^[4]. This dual risk makes the use of traditional “blood-thinning” medications like aspirin or anticoagulants highly complex; because these treatments can prevent blockages but may increase the risk of a bleed, they must be managed with caution and highly individualized by a specialized neurology team ^[4][5]. Crucially, you should never start, stop, or adjust these medications on your own without your prescribing clinician.

Because CARASAL is so rare, diagnosis often relies on finding specific “clues” that distinguish it from similar conditions. Beyond confirming a pathogenic genetic variant, specialists look for prominent involvement of the pons (a part of the brainstem) on MRI scans and a supportive physical feature called enophthalmos, where the eyes appear slightly deep-set ^[4]. This is often visible on imaging as the “orbital check-mark sign,” a marker that, when present, helps support the diagnosis and ensures that your care is tailored specifically to the unique biological needs of CARASAL ^[4]. Oriented by these findings, you and your care team can focus on the most effective ways to protect your vascular health and manage the long-term journey.