Hereditary cystatin C amyloid angiopathy

Hereditary Cystatin C Amyloid Angiopathy

Crystal structure of human cystatin C monomer

Hereditary cystatin C amyloid angiopathy (HCCAA) is a rare genetic disorder characterized by the deposition of amyloid in the cerebral blood vessels. This condition is primarily associated with mutations in the CST3 gene, which encodes the protein cystatin C.

Pathophysiology

Cystatin C is a cysteine protease inhibitor that plays a crucial role in regulating proteolytic activity in the body. In HCCAA, a specific mutation in the CST3 gene leads to the production of an abnormal form of cystatin C. This mutant protein is prone to misfolding and aggregation, resulting in the formation of amyloid deposits in the walls of cerebral blood vessels. These deposits can lead to cerebral amyloid angiopathy, which increases the risk of intracerebral hemorrhage.

Clinical Presentation

Patients with HCCAA typically present with recurrent cerebral hemorrhages, often beginning in early adulthood. The condition is characterized by a progressive decline in neurological function, which may include stroke, dementia, and other cognitive impairments. The recurrent hemorrhages are often fatal, and the average life expectancy is significantly reduced.

Diagnosis

The diagnosis of HCCAA is based on clinical presentation, family history, and genetic testing. Imaging studies such as MRI and CT scan can reveal cerebral hemorrhages and other changes consistent with amyloid angiopathy. Genetic testing can confirm the presence of the CST3 gene mutation.

Treatment

Currently, there is no cure for HCCAA. Treatment is primarily supportive and focuses on managing symptoms and preventing complications. This may include the use of antihypertensive drugs to control blood pressure and reduce the risk of hemorrhage. Genetic counseling is recommended for affected families.

Prognosis

The prognosis for individuals with HCCAA is generally poor due to the high risk of recurrent cerebral hemorrhages. The condition often leads to severe neurological impairment and early death. Research is ongoing to better understand the disease mechanism and develop potential therapies.

Related Pages

• Cerebral amyloid angiopathy
• Cystatin C
• Intracerebral hemorrhage
• Genetic disorders