Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)

Last revised by Rohit Sharma on 13 Mar 2024

Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is a very rare monogenic autosomal dominant cerebral small vessel disease.

CARASAL is considered extremely rare, with less than thirty cases reported in the literature 1-5. The condition tends to clinically manifest in the third to fifth decades of life 2.

The potential clinical manifestations are varied and may be mild for the degree of radiographic changes 1-5:

  • focal neurological deficits from stroke

  • migraine-like headache

  • cognitive impairment and dementia

  • movement disorders, e.g. gait disorder, dystonia

  • vestibulocochlear symptoms

Extracranial clinical manifestations may also be seen, although, given the rarity of the condition, it is unclear if these are due to CARASAL or are simply seen in association 1-5:

CARASAL is caused by a point mutation (c.973C>T) in the CTSA gene, located within chromosome 20q13.12, which encodes for cathepsin A 1-4. This mutation is inherited in an autosomal dominant pattern 1-5. It is yet to be fully elucidated how this mutation leads to the clinicoradiological syndrome that is observed in CARASAL 1,5.

Notably, this is condition is very distinct from autosomal recessive mutations in CTSA implicated in the lysosomal storage disorder galactosialidosis 2.

MRI is the imaging modality of choice and demonstrates the following features 1-5:

No specific disease-modifying treatment is currently available and symptomatic management and specialist screening is recommended 1. It is thought that life expectancy is similar to that of an unaffected individual 4.

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