Cause
CARASIL is caused by mutation of the HTRA1 gene which encodes the HtrA serine peptidase 1 protein (HTRA1). HTRA1 is located on chromosome 10 and encodes an enzyme that regulates signaling by the TGF-β family of proteins. TGF-β protein family plays an important role in cellular functions, especially in angiogenesis. Individuals with CARASIL have mutations in HTRA1 which leads to a reduced amount of HTRA1 protein or no HTRA1 protein at all. The mutant proteins are unable to suppress TGF-β activity. Increase in TGF-β1 activity has been seen in the tunica media of affected small arteries.CARASIL is an autosomal recessive disease, meaning that both parents must be a carrier for the allele in order for the disease to be passed on to the child. As with other autosomal recessive diseases, the likelihood of receiving a recessive allele from both parents increases if the parents are closely related to each other (consanguineous). This trend has been observed for CARASIL. Pathophysiology
A few different types of mutations to the HTRA1 gene have been observed in CARASIL patients. Nonsense mutations have been shown to cause no HTRA1 protein to be produced, while missense mutations have been shown to produce some HTRA1 protein, but with reduced activity. Regardless of whether or not HTRA1 protein is produced, or its activity is greatly reduced, the normal regulatory activity of the HTRA1 protein is lost. This means that TGF-β (transforming growth factor beta) signaling cannot be repressed as normal.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is disease of the arteries in the brain, which causes tissue loss in the subcortical region of the brain and the destruction of myelin in the CNS. CARASIL is characterized by symptoms such as gait disturbances, hair loss, low back pain, dementia, and stroke. CARASIL is a rare disease, having only been diagnosed in about 50 patients, of which ten have been genetically confirmed. Most cases have been reported in Japan, but Chinese and caucasian individuals have also been diagnosed with the disease. CARASIL is inherited in an autosomal recessive pattern. There is currently no cure for CARASIL. Other names for CARASIL include familial young-adult-onset arteriosclerotic leukoencephalopathy with alopecia and lumbago without arterial hypertension, Nemoto disease  and Maeda syndrome. Signs and symptoms
Symptoms of CARASIL may include spondylosis deformans, lumbago (lower back pain) due to herniated disks, alopecia, spasticity in the limbs leading to gait disturbances, dysarthria, urinary incontinence, pseudobulbular signs, arteriosclerosis of cerebral arteries, mood changes, stroke, and dementia.Individuals with CARASIL may experience spondylosis and alopecia beginning in their teens, although alopecia is not seen in all patients. Other signs of the disease, particularly neurological abnormalities, may present from ages 20-40 with symptoms worsening over time. About 50% of affected patients present with stroke, and most strokes experienced by patients are lacunar infarcts. Many patients experience some form of mood changes, personality disorders, and/or dementia over time.