CARASAL

Not to be confused with CARASIL or CADASIL.

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 preasure.^[3]

Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy
Other names	CARASAL
CARASAL is inherited in an autosomal dominant fashion.

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.^[4]

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

Cause

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.^[7][5]

According to some studies, the c.973C→T (p.R325C) mutation is associated with that disorder.^[8][2]

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.^[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.^[10][11]

As mentioned at the beginning of the article, CARASAL is allelic to Galactosialidosis, although Galactosialidosis is an autosomal recessive disorder.^[2][12]

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: ^[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.

Treatment

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

Prognosis

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

History

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

See also

• CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts And Leukoencephalopathy)
• CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)