Nasu-Hakola disease;
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-hakola disease is an autosomal recessive inherited disorder. It is characterized by repeated fractures occurring during adolescence and progressive presenile dementia in the fourth decade. The disease is caused by a mutation in the TREM2 or DAP12 gene that regulates osteoclast differentiation. TREM2-DAP12 is also expressed by microglia, thus neurological impairments seen in this disease are considered to be directly caused by microglial dysfunstion.

Congenital disorder of metabolism

(PLOSL1) DAP12 [HSA:7305] [KO:K07992]
(PLOSL2) TREM2 [HSA:54209] [KO:K14378]

PMID:20500450

Kaneko M, Sano K, Nakayama J, Amano N

Nasu-Hakola disease: The first case reported by Nasu and review: The 50th Anniversary of Japanese Society of Neuropathology.

Neuropathology 30:463-70 (2010)
DOI:10.1111/j.1440-1789.2010.01127.x

PMID:20836191

Bianchin MM, Martin KC, de Souza AC, de Oliveira MA, Rieder CR

Nasu-Hakola disease and primary microglial dysfunction.

Nat Rev Neurol 6:2 p following 523 (2010)
DOI:10.1038/nrneurol.2010.17-c1

PMID:20301376

Paloneva J, Autti T, Hakola P, Haltia MJ

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL)

GeneReviews (1993)