• Nasu-Hakola disease
• genetics

Polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy (PLOSL; MIM 221770), also known as Nasu-Hakola disease, is a recessively inherited disorder characterised by systemic bone cysts and progressive presenile dementia associated with sclerosing leucoencephalopathy.¹ The onset usually occurs in the third decade of life with pathological fractures; later on, symptoms of frontal lobe dysfunction appear, with upper motor neurone involvement and epileptic seizures. Some patients, however, do not have clinically manifest osseous problems despite the radiological demonstration of cystic bone lesions. The disease leads to death before the age of 50.¹

The disease is characterised by genetic heterogeneity: mutations in two genes (TYROBP and TREM2) encoding different subunits of a membrane receptor complex in natural killer and myeloid cells have been associated with the disease.^2,3

This rare disorder was initially described in Finland and Japan but is now recognised to have a worldwide distribution.¹ In particular, sporadic cases have been described in Italy,^4,5 and a homozygous mutation in the splice donor consensus site at intron 3 of TREM2 has been identified in two affected siblings.³

We report here the clinical and genetic analysis of an Italian family in which two siblings are affected by PLOSL.