View source for Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

{{Infobox medical condition (new)
| name            = Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
| synonyms        = Nasu-Hakola disease
| image           =
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| pronounce       =
| field           = [[Medical genetics]]
| symptoms        =
| complications   =
| onset           =
| duration        =
| types           =
|causes           = mutations in either the ''[[TYROBP]]'' or ''[[TREM2]]'' genes
|risks           = <!-- or |risk= -->
|diagnosis       = frontal atrophy of the cerebral white matter, multifocal cystic lesions on the bones of hands, wrists, feet and ankles
|differential    = frontal-type dementia and polycystic bone lesions in the fourth decade of life
|prevention      =
|treatment       = <!-- or |management= -->
|medication      =
|prognosis       = fatal in the fifth decade of life
|frequency       = 1 in 500,000 to 1,000,000
| deaths          =
}}
'''Nasu–Hakola disease''' also known as '''polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy''' is a rare disease characterised by early-onset dementia and multifocal bone cysts.<ref name=Kondo2002>{{cite journal | vauthors = Kondo T, Takahashi K, Kohara N, Takahashi Y, Hayashi S, Takahashi H, Matsuo H, Yamazaki M, Inoue K, Miyamoto K, Yamamura T | title = Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms | journal = Neurology | volume = 59 | issue = 7 | pages = 1105–7 | date = October 2002 | pmid = 12370476 | doi = 10.1212/wnl.59.7.1105 | s2cid = 36364470 }}</ref> It is caused by [[autosomal recessive]] loss of function mutations in either the ''[[TREM2]]'' or ''[[TYROBP]]'' gene that are found most frequently in the Finnish and Japanese populations.<ref name="Paloneva_2020" />
==Signs and symptoms==
Four stages are recognised in this condition. The first (latent stage) show no symptoms or signs. This stage typically lasts up to the early 20s. This is followed by the osseous stage. This is characterised by recurrent bone pain usually affecting the long bones of the limbs. This is usually followed by [[pathological fracture]]s of these bones. The third stage (early neurological) is marked by the onset of symptoms typical of a [[frontal lobe syndrome]] ([[euphoria]], lack of concentration, loss of judgment and social inhibitions) with memory loss. [[Epilepsy]] may occur. This stage usually has its onset in the late 20s and early 30s. The final stage is characterised by severe dementia and paralysis. Death usually occurs in the late 40s or early 50s.{{cn|date=November 2020}}
==Genetics==
This condition has been associated with mutations in the TYRO protein tyrosine kinase binding protein (''[[TYROBP]]'') gene and in the triggering receptor expressed on myeloid cells 2 (''[[TREM2]]'') gene. ''TYROBP'' is located on the long arm of [[chromosome 19]] (19q13.12) and ''TREM2'' is located on short arm of [[chromosome 6]] (6p21.1).<ref name="Paloneva_2020">{{cite book | vauthors = Paloneva J, Autti T, Hakola P, Haltia MJ | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Mirzaa G, Amemiya A | chapter = Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy | title = GeneReviews | location = Seattle (WA) | publisher = University of Washington, Seattle | date = December 2020 | pmid = 20301376 | doi = | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK1197/ }}</ref>
==Pathopysiology==
This is not understood but appears to involve the [[microglia]].{{cn|date=November 2020}}
==Diagnosis==
This syndrome may be suspected on clinical grounds. The diagnosis is established by sequencing the ''TYROBP'' and ''TREM2'' genes.{{cn|date=November 2020}}
===Differential diagnosis===
* [[Frontotemporal dementia]]
===Investigations===
X rays show the presence of bone cysts and [[osteoporosis]]. [[CT scan|CT]] or [[Magnetic resonance imaging|MRI]] of the brain show loss of tissue in the [[frontotemporal lobe]]s of the brain. Calcification of the [[basal ganglia]] is common. [[Electroencephalography|EEG]] is typically normal initially but diffuse slowing and irritative activity later.{{cn|date=November 2020}}
==Treatment==
There is no specific treatment for this condition. Management is supportive.{{cn|date=November 2020}}
==Epidemiology==
This condition is considered to be rare, with ~200 cases described in the literature. The estimated population prevalence is 2.0 x 10<sup>−6</sup> in Finns.{{cn|date=November 2020}}
==History==
This condition was first described in 1973.<ref name=Nasu1973>{{cite journal | vauthors = Nasu T, Tsukahara Y, Terayama K | title = A lipid metabolic disease-"membranous lipodystrophy"-an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues | journal = Acta Pathologica Japonica | volume = 23 | issue = 3 | pages = 539–58 | date = August 1973 | pmid = 4800725 | doi = 10.1111/j.1440-1827.1973.tb01223.x | s2cid = 9720550 | url = }}</ref><ref name=Hakola1973>{{cite journal | vauthors = Hakola HP, Iivanainen M | title = A new hereditary disease with progressive dementia and polycystic osteodysplasia: neuroradiological analysis of seven cases | journal = Neuroradiology | volume = 6 | issue = 3 | pages = 162–8 | date = November 1973 | pmid = 4764488 | doi = 10.1007/BF00340444 | s2cid = 19306332 }}</ref>
==References==
{{Reflist}}
[[Category:Genetic diseases and disorders]]
[[Category:Rare syndromes]]