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.
Categories
Specialists separate autoimmune thyroiditis into two clinical categories. If goiters are present, it is understood as Hashimotos thyroiditis. If the thyroid is atrophic, and does not present goiters, it is called atrophic thyroiditis.Autoimmune thyroiditis can also refer to Graves disease, and various other forms of thyroid illnesses. If the symptoms of thyroiditis appear in women after giving birth, it is called postpartum thyroiditis. Diagnosis
Various tests can be chosen depending on the presenting symptoms. Doctors may search for Thyroid peroxidase Antibodies (TPOAb) when a person has symptoms of hypothyroidism, or when a person will be started on a drug therapy associated with risks of developing hypothyroidism, such as lithium or Interferon alfa. This antibody is related to Hashimotos thyroiditis and Graves disease. If the person presents symptoms of hyperthyroidism, doctors are more likely to test for Thyroid stimulating hormone receptor Antibodies (TRAb), and monitor the effects of anti-thyroid therapy, also associated with Graves disease.Doctors may check Thyroglobulin Antibodies (TgAb) also, whenever a thyroglobulin test is performed to see if the antibody is interfering. TgAb may also be ordered in regular intervals after a person has been diagnosed with thyroid cancer, and just like TPOAb, it can be associated with Hashimotos thyroiditis. Treatment
The usual therapy is Levothyroxine. References


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