Cystatin C amyloid angiopathy

Hereditary cystatin C amyloid angiopathy (HCCAA), a rare genetic disorder. People with HCCAA have an average life expectancy of just 30 years, and most die within five years of their first stroke.

HCCAA is an inherited disease, caused by a leucine 68 to glutamine variant of human cystatin C known as L68Q-hCC. Young people with the L68Q-hCC mutation suffer from microinfarcts, which are microscopic lesions, or areas of cellular death or tissue necrosis that are associated with cognitive impairment in older adults. Cerebral microinfarcts are clinical markers for stroke and dementia. In people with HCCAA, the microinfarcts begin in their 20s along with brain hemorrhages, leading to paralysis, dementia and — as the strokes become more frequent — death. hCC protein deposits are found primarily in the brain in those with HCCAA, though they may also be found in other internal organs.

The average lifespan of those affected has dropped significantly, from approximately 65 years in 1825 to about 30 years in 2021. Lifestyle, economic and industrial changes have all been suggested as contributing factors to this decline, including increased consumption of carbohydrates in the diet.