Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, also called Nasu-Hakola disease and abbreviated PLOSL, is a rare progressive disorder that affects both the bones and the brain. Cyst-like changes in the bones bring persistent pain and pathological fractures, appearing first in the hands, feet, wrists and ankles. Later stages bring frontal lobe symptoms such as euphoria, poor concentration and loss of judgment, with memory loss, and then severe dementia and paralysis; death usually occurs in the late forties or early fifties. The disease is caused by autosomal recessive loss-of-function mutations in either the TREM2 or the TYROBP gene and is found most often in Finnish and Japanese populations, with about 200 cases described in the literature. Diagnosis rests on the bone and neurological findings and can be confirmed by genetic testing. There is no cure, although bone grafts can temporarily treat the cysts and pain.