Nasu–Hakola Disease (Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy—PLOSL): A Dementia Associated with Bone Cystic Lesions. From Clinical to Genetic and Molecular Aspects

@article{Bianchin2004NasuHakolaD,
  title={Nasu–Hakola Disease (Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy—PLOSL): A Dementia Associated with Bone Cystic Lesions. From Clinical to Genetic and Molecular Aspects},
  author={Marino Muxfeldt Bianchin and Heraldo Macuco Capella and Daniel Loureiro Chaves and Mario Steindel and Edmundo Carlos Grisard and Gerson Gandi Ganev and Jo{\~a}o P{\'e}ricles Jr. da Silva and Evaldo Schaeffer Neto and M{\^o}nica Aparecida Poffo and Roger Walz and Carlos Gilberto Jr. Carlotti and Am{\'e}rico Ceiki Sakamoto},
  journal={Cellular and Molecular Neurobiology},
  year={2004},
  volume={24},
  pages={1-24}
}
The authors review the clinical, radiological, electrophysiological, pathological, and molecular aspects of Nasu–Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy or PLOSL). Nasu-Hakola disease is a unique disease characterized by multiple bone cysts associated with a peculiar form of neurodegeneration that leads to dementia and precocious death usually during the fifth decade of life. The diagnosis can be established on the basis of clinical and… 

Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease

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Interestingly, significant DAP 12 expression was found in numerous microglia in one NHD case with a homozygous DAP12 single-base substitution, and both real-time PCR and Western blotting confirmed the finding.

Extremity Manifestations and Surgical Treatment for Nasu Hakola Disease

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The aim in this study is to show the beneficial aspect of surgical intervention in the cystic lesions of Nasu Hakola disease in the skeleton to obtain the patient a painless joint although surgery is rarely performed in this systemic and progressive disease.

Targeted sequencing approach to identify genetic mutations in Nasu-Hakola disease.

TLDR
Targeted resequencing of genetic mutations of seven NHD cases with known molecular diagnosis and two control subjects indicates that targeted sequencing is a useful approach to precisely identify genetic mutations responsible for NHD in a comprehensive manner.

Possible role of microgliopathy in the pathogenesis of Nasu–Hakola disease

TLDR
Observations suggest that TREM2 expression on microglia in vivo is a transient event, depending on their microenvironment, and presently undefined non‐TREM2/DAP12 signaling pathways positively regulate activation of Syk in NHD brains.

Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia

TLDR
The results provide the first information about the expression, distribution, and functioning of the TREM2/DAP12 system in nerve cells, a necessary step in the understanding of the cellular mechanisms affected in polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy.

Alzheimer's disease pathology in Nasu-Hakola disease brains.

TLDR
The expression of Aβ and phosphorylated tau (p-tau) in the frontal cortex and the hippocampus of five NHD cases were studied and several small Aβ-immunoreactive spheroids, almost undetectable in NHD brains were identified.

Immunohistochemical characterization of CD33 expression on microglia in Nasu‐Hakola disease brains

  • J. SatohY. Kino K. Arima
  • Biology
    Neuropathology : official journal of the Japanese Society of Neuropathology
  • 2015
TLDR
Results do not support the view that CD33‐expressing microglia play a central role in the development of leukoencephalopathy in NHD brains, and CD33 expression patterns in five N HD brains and 11 controls by immunohistochemistry are studied.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

Immunohistochemical characterization of microglia in Nasu‐Hakola disease brains

TLDR
Allograft inflammatory factor 1 (AIF1, Iba1) and sialic acid binding Ig‐like lectin 1 (SIGLEC1) are identified as putative NHD‐specific biomarkers by bioinformatics analysis of microarray data of NHD DC and characterized their expression on microglia in NHD brains.

Gene Expression Profile of THP-1 Monocytes Following Knockdown of DAP12, A Causative Gene for Nasu-Hakola Disease

TLDR
It is suggested that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD.
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CNS manifestations of Nasu–Hakola disease

TLDR
Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations, suggesting patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists.

CNS manifestations of Nasu–Hakola disease: A frontal dementia with bone cysts

TLDR
Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations, suggesting patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists.

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TLDR
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Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case

TLDR
The present case suggests that NHD also affects the thalamus, and an unusual pathological finding in this case was selective involvement of theThalamic nuclei with preservation of the other gray matter except for focal cortical necrosis.

Nasu-Hakola's disease (membranous lipodystrophy)

TLDR
The neuropathologic examination revealed marked symmetrical gliosis of the cerebral white matter predominantly in the frontal and temporal lobes with slight or moderate demyelination and widespread axonal changes such as fragmentation and spheroid in the white matter of the cortex, cerebellum, basal ganglia, and brain stem.

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TLDR
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TLDR
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OSTEODYSPLASIA POLYCYSTICA HEREDITARIA COMBINED WITH SCLEROSING LEUCOENCEPHALOPATHY

TLDR
The study of this disease reached a new phase when three sick siblings were found and the fatal progressive dementia was combined with this cystic osseous disease, and a frontal syndrome was found in all cases.

Ein Fall von “Membranöser Lipodystrophie (Nasu),” unter besonderer Berücksichtigung des psychiatrischen und neuropathologischen Befundes

TLDR
A housewife, 42 years old, died from a chronic progressive neuro-psychiatric illness characterized by memory disturbance, moria-syndrome, euphoria, social disorder and extrapyramidal symptoms combined with a severe bone disease, which showed a characteristic degeneration with "membranous cycle" structures.
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