CARASAL

Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy (CARASAL) is a rare genetic disorder that is caused by mutation in a gene CTSA which is located on a chromosome 20.¹ This disease is allelic to Galactosialidosis.² 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.³

Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy
Other names	CARASAL
CARASAL is inherited in an autosomal dominant fashion.
Symptoms	Migraine, mini-stroke, facial palsy, dementia, depression, concentration problems, movement problems, vertigo, difficulty swallowing, slurred speech, sicca symptoms, problems with REM sleep, drug-resistant hypertension
Usual onset	20s-40s
Causes	Genetic mutation
Diagnostic method	MRI, genetic testing
Prognosis	Normal life expectancy

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.⁴

This condition usually manifest in the third to fifth decades of life.⁵

CARASAL is caused by mutation of the CTSA which codes enzyme Cathespin A.⁵ CTSA gene is located on 20q13.12.⁶

This disease is inherited in autosomal dominant fashion, which means that mutation of one gene copy is enough to cause the disorder.⁷⁵

According to some studies, the c.973C→T (p.R325C) mutation is associated with that disorder.⁸²

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.⁹ 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.¹⁰¹¹

As mentioned at the beginning of the article, CARASAL is allelic to Galactosialidosis, although Galactosialidosis is an autosomal recessive disorder.²¹²

CARASAL can be diagnosed by MRI investigation and by confirmation of the mutation in CTSA gene, also CARASAL should be considered in case of: ¹³

• Middle-age patients with Cerebral Small Vessel Disease (cSVD).
• Positive family history of stroke.
• Broad, unexplained, infra/supratentorial white and grey matter hyperintensities (a.k.a. bright signals on MRI image).
• Neurotological problems.

This disease doesn't have a cure, although symptomatic management is available.¹

It is believed that life expectancy is similar to unaffected person.³

CARASAL was described in 5 French patients by Herve et al.¹⁴