CARASAL
Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy '' is a rare genetic disorder that is caused by mutation in a gene [Cathepsin A|CTSA] which is located on a chromosome 20. This disease is allelic to Galactosialidosis. This disease usually begins with a headache, decreased concentration, abnormalities in gait, lack of inhibition, also it usually presents with migraine, depression, vertigo and high blood pressure.
Symptoms
The signs of this disease are: migraine, mini-stroke, facial palsy, dementia, depression, problems with concentration and movements, vertigo, difficulty in swallowing, slurring of speech, sicca symptoms, problems with REM sleep and drug-resistant hypertension.This condition usually manifest in the third to fifth decades of life.
Cause
CARASAL is caused by mutation of the CTSA which codes enzyme Cathespin A. CTSA gene is located on 20q13.12.This disease is inherited in autosomal dominant fashion, which means that mutation of one gene copy is enough to cause the disorder.
According to some studies, the c.973C→T mutation is associated with that disorder.
Pathophysiology
Cathespin A is a lysosomal enzyme which main function is to form complex between β-galactosidase and Neurominidase 1 in lysosomes to protect them from degradation. Also it is known that Cathespin A degrades Endothelin-1 and consequently it is known that Endothelin-1 might cause inhibition of oligodendrocyte progenitor cell maturation and remyelination through reactive astrocytes mechanism.As mentioned at the beginning of the article, CARASAL is allelic to Galactosialidosis, although Galactosialidosis is an autosomal recessive disorder.
Diagnosis
CARASAL can be diagnosed by MRI investigation and by confirmation of the mutation in CTSA gene, also CARASAL should be considered in case of:- Middle-age patients with Cerebral Small Vessel Disease.
- Positive family history of stroke.
- Broad, unexplained, infra/supratentorial white and grey matter hyperintensities.
- Neurotological problems.
Treatment