LAUSR

Cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL) is an acronym that describes an ultra-rare, hereditary, cerebral small vessel disease. The aim is to summarize current knowledge and recent findings concerning phenotype, genotype, pathogenesis, diagnoses, and treatment options of CARASAL. The method used in the study is a systematic literature review. CARASAL is clinically characterized by a wide range of predominantly central nervous system abnormalities. These include migraine, stroke with central facial palsy, facial pain, non-positional vertigo, cognitive dysfunction with impaired concentration and behavioral disinhibition, REM-sleep behavioral disorder, and depression. CARASAL is caused by point mutations in CTSA encoding cathepsin-A. Cathepsin-A is a carboxypeptidase that associates with the lysosomal enzymes b-galactosidase and neuraminidase, promoting their stabilization. In addition, cathepsin-A degradates endothelin-1. CARASAL is a primary microangiopathy with severe atherosclerosis of arterioles and secondary leukoencephalopathy. So far, 19 patients have been reported. The frequency of CARASAL patients will most likely increase in the future, as CARASAL may be more frequently recognized with the increasingly available methods for genetic testing and advanced imaging techniques. The phenotypic and genotypic spectrum of CARASAL needs to be more extensively investigated and animal models for the disease need to be generated. Currently, the outcome cannot be sufficiently assessed, as too few cases have been reported.