polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
MIM.221770 19q13.1, 6p21.2
Thursday 29 November 2007
Nasu Hakola disease (NHD) is a progressive dementia that presents accompanied by bone cysts and, at random, epilepsy. It is an autosomal recessive hereditary disease and its genetic defect is located at the 19q13.1 chromosome.
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) can be caused by loss-of-function mutations in the TYROBP gene (MIM.604142), also known as DAP12. Some patients with PLOSL have mutations in the TREM2 gene (MIM.605086).
The genetic mutation was identified at DAP12. It appears that DAP12 is expressed in the microglial activation and the differentiation of macrophages in the central nervous system and, at the same time, in the osteoclasts in charge of bone remodelling.
This double character consisting of dementia and bone cysts, which contain triglycerides and thin PAS positive membranes in a bone with cortical erosion and medullary hypoplasia, enables us to differentiate this disease from other frontotemporal neurodegenerative disorders, such as Pick s disease.
prion diseases (variant Creutzfeldt-Jakob)