title: Nasu-Hakola disease: a rare entity in Italy. Critical review of the literature.
abstract: Nasu-Hakola disease (NHD, polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, PLOSL) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile dementia associated with sclerosing encephalopathy. The disease has a worldwide distribution, but most patients have been reported in Finland and in Japan; in Italy there are anecdotal reports. The combination of neuropsychiatric symptoms and bone cysts is unique to this disease, which we believe to be underestimated in Italy. The molecular defect has been identified in loss-of-function mutations in the TYROBP gene in Finnish and in Japanese patients, and in the TREM2 gene in other families of different ethnic origins. We reviewed the international literature to define better the diagnostic steps and to draw the attention of neurologists and orthopaedic specialists to the disease. The identification of new cases followed by appropriate genetic counselling, genetic analysis, and study of the territorial distribution of affected patients could be a good strategy to follow in order to improve understanding of the disease.
authors.affiliation: Department of Neuroscience, University of Pavia, IRCCS "C. Mondino Institute of Neurology" Pavia, Italy. lmontalb@unipv.it
authors.forename: Lorenza
authors.initials: L
authors.lastname: Montalbetti
authors.forename: Debora
authors.initials: D
authors.lastname: Soragna
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ratti
authors.forename: Paola
authors.initials: P
authors.lastname: Bini
authors.forename: Simona
authors.initials: S
authors.lastname: Buscone
authors.forename: Arrigo
authors.initials: A
authors.lastname: Moglia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001845:Bone Cysts / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D003704:Dementia / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008060:Lipodystrophy / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D010009:Osteochondrodysplasias / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D011971:Receptors, Immunologic / Q000235:genetics; D013344:Subacute Sclerosing Panencephalitis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D013577:Syndrome; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C110546:TYROBP protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1