Raras
Buscar doenças, sintomas, genes...
Doença de Nasu-Hakola
ORPHA:2770CID-10 · G31.8CID-11 · 8A44.3DOENÇA RARA

Leucodistrofia hereditária rara caracterizada por demência pré-senil progressiva associada a fraturas ósseas recorrentes devido a lesões ósseas policísticas das extremidades inferiores e superiores.

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Introdução

O que você precisa saber de cara

📋

Leucodistrofia hereditária rara caracterizada por demência pré-senil progressiva associada a fraturas ósseas recorrentes devido a lesões ósseas policísticas das extremidades inferiores e superiores.

Publicações científicas
188 artigos
Último publicado: 1993

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
<1 / 1 000 000
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.0
Europe
Início
Adolescent
+ adult
🏥
SUS: Cobertura mínimaScore: 15%
CID-10: G31.8
🇧🇷Dados SUS / DATASUS
PROCEDIMENTOS SIGTAP (2)
0202010694
Sequenciamento completo do exoma (WES)genetic_test
0301070040
Atendimento em reabilitação — doenças rarasrehabilitation
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧠
Neurológico
15 sintomas
🦴
Ossos e articulações
8 sintomas
🫘
Rins
2 sintomas
❤️
Coração
1 sintomas
🫃
Digestivo
1 sintomas
💪
Músculos
1 sintomas

+ 29 sintomas em outras categorias

Características mais comuns

90%prev.
Atrofia cortical cerebral
Muito frequente (99-80%)
90%prev.
Demência do lobo frontal
Muito frequente (99-80%)
90%prev.
Alterações de personalidade
Muito frequente (99-80%)
90%prev.
Cisto ósseo
Muito frequente (99-80%)
90%prev.
Ventriculomegalia
Muito frequente (99-80%)
90%prev.
Anormalidade da morfologia da epífise
Muito frequente (99-80%)
57sintomas
Muito frequente (17)
Frequente (8)
Ocasional (3)
Sem dados (29)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 57 características clínicas mais associadas, ordenadas por frequência.

Atrofia cortical cerebralCerebral cortical atrophy
Muito frequente (99-80%)90%
Demência do lobo frontalFrontal lobe dementia
Muito frequente (99-80%)90%
Alterações de personalidadePersonality changes
Muito frequente (99-80%)90%
Cisto ósseoBone cyst
Muito frequente (99-80%)90%
VentriculomegaliaVentriculomegaly
Muito frequente (99-80%)90%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico188PubMed
Últimos 10 anos103publicações
Pico201713 papers
Linha do tempo
2026Hoje · 2026📈 2017Ano de pico🧪 2021Primeiro ensaio clínico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

2 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.

TREM2Triggering receptor expressed on myeloid cells 2Disease-causing germline mutation(s) (loss of function) inTolerante
FUNÇÃO

Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:10799849). Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia (PubMed:27477018, PubMed:29518356). Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro-inflammatory cytokines, such as IL6R and CCL3, a

LOCALIZAÇÃO

Cell membraneSecreted

VIAS BIOLÓGICAS (4)
DAP12 signalingDAP12 interactionsOther semaphorin interactionsImmunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
MECANISMO DE DOENÇA

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2

An autosomal recessive disease characterized by presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years.

EXPRESSÃO TECIDUAL(Ubíquo)
Brain Spinal cord cervical c-1
47.7 TPM
Substância negra
20.1 TPM
Pulmão
17.4 TPM
Nervo tibial
14.5 TPM
Hipotálamo
10.7 TPM
OUTRAS DOENÇAS (8)
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2amyotrophic lateral sclerosisprogressive non-fluent aphasiabehavioral variant of frontotemporal dementia
HGNC:17761UniProt:Q9NZC2
TYROBPTYRO protein tyrosine kinase-binding proteinDisease-causing germline mutation(s) (loss of function) inTolerante
FUNÇÃO

Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:10604985, PubMed:9490415, PubMed:9655483). TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:9490415). Also has an inhibitory role in

LOCALIZAÇÃO

Cell membrane

VIAS BIOLÓGICAS (6)
DAP12 signalingDAP12 interactionsOther semaphorin interactionsSignal regulatory protein family interactionsNeutrophil degranulation
MECANISMO DE DOENÇA

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1

A recessively inherited disease characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usually leads to death in the fifth decade of life.

EXPRESSÃO TECIDUAL(Ubíquo)
Sangue
1786.3 TPM
Baço
563.6 TPM
Pulmão
404.2 TPM
Adipose Visceral Omentum
142.5 TPM
Tecido adiposo
131.6 TPM
OUTRAS DOENÇAS (2)
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly
HGNC:12449UniProt:O43914

Variantes genéticas (ClinVar)

63 variantes patogênicas registradas no ClinVar.

🧬 TREM2: NM_018965.4(TREM2):c.491T>A (p.Leu164Ter) ()
🧬 TREM2: NM_018965.4(TREM2):c.428del (p.Phe143fs) ()
🧬 TREM2: NM_018965.4(TREM2):c.41-1G>C ()
🧬 TREM2: NM_018965.4(TREM2):c.114T>G (p.Tyr38Ter) ()
🧬 TREM2: NM_018965.4(TREM2):c.257A>T (p.Asp86Val) ()
Ver todas no ClinVar

Diagnóstico

Os sinais que médicos procuram e os exames que confirmam

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Tratamento e manejo

Remédios, cuidados de apoio e o que precisa acompanhar

Carregando informações de tratamento...

Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Doença de Nasu-Hakola

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Selecione um estado ou use sua localização para ver resultados.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

Pesquisa ativa

Ensaios clínicos abertos e novidades científicas recentes

Pesquisa e ensaios clínicos

Nenhum ensaio clínico registrado para esta condição.

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Publicações mais relevantes

Timeline de publicações
104 papers (10 anos)
#1

A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.

Neurology India2026 Mar 01

Triggering Receptor expressed on Myeloid cells 2 (TREM2) mutations can cause Nasu-Hakola disease, a rare form of dementia, and are also linked to an increased risk of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The TREM2 receptor plays a role in microglial cell function, including response to injury and amyloid beta pathology in the brain. Variants in TREM2, particularly in exon 2, can disrupt its function, contributing to AD pathology, such as accumulation of amyloid beta plaques and tau tangles. In this study, we conducted screening of exon 2 in TREM2 to identify mutations in a carefully characterized cohort comprising individuals with AD, FTD, and mild cognitive impairment (MCI) from South India. We report the identification of a homozygous p.R47C variant (rs753325601) in a case diagnosed with frontal variant AD. Our finding reinforces the correlation between TREM2 genetic variations and the manifestation of atypical AD phenotypes, highlighting the significance of TREM2 mediated pathogenic mechanisms in modulating disease presentation.

#2

System biology and network-based approach to identify the therapeutic signatures and potential inhibitors against polycystic lipomembranous osteodysplasia with Sclerosing Leukoencephalopathy.

PloS one2026

Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), often recognized as Nasu-Hakola disease, is an uncommon autosomal recessive systemic condition described by numerous bone lesions that resemble cysts and progressive early-onset dementia. One novel way to find possible drug targets is to use Network Analyst tools for network-based gene expression profiling. Identifying the target hub genes, essential for the initiation and progression of PLOSL, is validated by the significance level (p-score) attained using Cytoscape in the survival analysis of the major central genes. The X2K online tool also examined the regulatory kinases that formed the interaction between protein molecule networks. Out of the 53 genes obtained to be differentially expressed, PPARG and AIF1 had the greatest degree score, followed by C1QA with 5 degrees and SIGLEC1 and MSR1 with 4 degrees. Furthermore, Molecular docking of target PPARG gene with AMG-131 and Elafibranor drugs, having the chemical formulas 2-[2,6-dimethyl-4-[(E)-3-(4-methylsulfanylphenyl)-3-oxoprop-1-enyl]phenoxy], and 3,5-dichloro-4-quinolin-3-yloxyphenyl) benzenesulfonamide, along control (Rosiglitazone (S) shows binding affinities of -7.2 kcal/mol, -7.4 kcal/mol, and -7.6 kcal/mol respectively. The enzyme remained extremely stable in the complex throughout 200 ns, with a mean Root Mean Square Deviation (RMSD) of 2.95 Å for the AMG-131 complex system and 2.93 Å against the Elafibranor complex system. Root Mean Square Fluctuation (RMSF) anticipated steady behavior with average RMSD for the active site residues in the docked system. Arg76 and Leu28leu Leu118 were shown to be essential enzyme residues for binding, anchoring, and bridging strong hydrogen and hydrophobic interactions between the enzyme and the inhibitor, according to the Radial Distribution Function (RDF). These results broadened our knowledge of putative biomarkers for PLOSL diseases, and an experimental strategy will improve our results even more in the future.

#3

TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting.

International journal of molecular sciences2025 Jul 22

TREM2 (triggering receptor expressed on myeloid cells 2) is a membrane-bound receptor primarily expressed on microglia in the central nervous system (CNS). TREM2 plays a crucial role in regulating immune responses, phagocytosis, lipid metabolism, and inflammation. Mutations in the TREM2 gene have been linked to various neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and Nasu-Hakola disease (NHD). These mutations are suggested to impair microglial activation and reduce the ability to clear amyloid aggregates, leading to exacerbated neuroinflammatory responses and accelerating disease progression. This review provides an overview of TREM2 structure, functions, and known pathogenic variants-including Arg47His, Arg62His, His157Tyr, Tyr38Cys, and Thr66Met. Furthermore, the molecular and cellular consequences of TREM2 mutations are introduced, such as impaired ligand binding, altered protein folding and trafficking, enhanced TREM2 shedding, and dysregulated inflammatory signaling. We also highlight recent advances in therapeutic strategies aimed at modulating TREM2 signaling. These include monoclonal antibodies (e.g., AL002, CGX101), small molecule agonists, and gene/cell-based therapies that seek to restore microglial homeostasis, enhance phagocytosis, and reduce neuroinflammation. While these approaches show promise in in vivo/in vitro studies, their clinical translation may be challenged by disease heterogeneity and mutation-specific responses. Additionally, determining the appropriate timing and precise dosing will be essential.

#4

Neuroglia in leukodystrophies.

Handbook of clinical neurology2025

Leukodystrophies are a heterogeneous group of rare genetic neurologic disorders characterized by white matter degeneration resulting from mutations affecting glial cells. This review focuses on the primary subtypes-astroglial, oligodendroglial, and microglial leukodystrophies-offering a detailed description of their neuropathologic features and clinical manifestations. It delves into key aspects of the pathogenesis, emphasizing the distinct cellular mechanisms that drive white matter damage. Advances in disease modeling, including the development of animal models with pathologic gene expressions and patient-derived iPS-cell models, have significantly enhanced our understanding of these rare disorders. Insights into the roles of different glial cell types highlight the complexity of leukodystrophies and provide a foundation for the development of targeted therapeutic strategies.

#5

Generation of a human induced pluripotent stem cell line (BIHi292-A) from PBMCs of a female patient diagnosed with Nasu-Hakola disease (NHD)/polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) carrying a novel heterozygous mutation in the TREM2 gene.

Stem cell research2025 Mar

NHD/PLOSL is an orphan disease characterized by progressive presenile dementia associated with recurrent fractures due to polycystic bone lesions. In this study, we generated the human induced pluripotent stem cell (hiPSC) line BIHi292-A from a 30-year-old women diagnosed with NHD/PLOSL, carrying two compound heterozygous frameshift mutations [c.313del (p.Ala105fs) and c.199del (p.His67fs)] in the TREM2 (triggering receptor expressed on myeloid cells 2) gene. BIHi292-A hiPSCs are karyotypically normal, express typical markers for the undifferentiated state and have pluripotent differentiation potential. BIHi292-A cells will provide a valuable tool for investigating pathogenic mechanisms of NHD/PLOSL and TREM2-related research questions.

Publicações recentes

Ver todas no PubMed

📚 EuropePMC83 artigos no totalmostrando 101

2026

A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.

Neurology India
2026

System biology and network-based approach to identify the therapeutic signatures and potential inhibitors against polycystic lipomembranous osteodysplasia with Sclerosing Leukoencephalopathy.

PloS one
2025

Nasu-Hakola Disease Presenting as Rapidly Progressive Dementia With Seizures: A TREM2 Mutation Case Without Skeletal Involvement.

Cureus
2025

Roles of TREM2 in Alzheimer's disease.

Translational neurodegeneration
2025

Nasu-Hakola Disease: Crippling the Brain and Bones!

Annals of Indian Academy of Neurology
2025

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy: report of two cases.

Dementia &amp; neuropsychologia
2025

TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting.

International journal of molecular sciences
2025

Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease.

Computational and structural biotechnology journal
2025

Neuroglial Pathophysiology of Leukodystrophies.

Advances in neurobiology
2025

Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease.

Molecular neurodegeneration
2025

Neuroglia in leukodystrophies.

Handbook of clinical neurology
2025

TREM2 in Regulating Macrophage Inflammatory Responses and Disease Pathogenesis.

Critical reviews in immunology
2025

Generation of a human induced pluripotent stem cell line (BIHi292-A) from PBMCs of a female patient diagnosed with Nasu-Hakola disease (NHD)/polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) carrying a novel heterozygous mutation in the TREM2 gene.

Stem cell research
2025

Extracellular domain of TREM2 possess two distinct ligand recognition sites: Insights from machine-learning guided docking and all-atoms molecular dynamics simulations.

Heliyon
2024

Engineering of Human Blood-Induced Microglia-like Cells for Reverse-Translational Brain Research.

Journal of visualized experiments : JoVE
2024

Microglia in Neurodegenerative Diseases.

Advances in neurobiology
2024

Behavioral variant of frontotemporal dementia in carriers of biallelic TREM2 variants: cases study.

Folia neuropathologica
2024

DAP12 interacts with RER1 and is retained in the secretory pathway before assembly with TREM2.

Cellular and molecular life sciences : CMLS
2024

Homozygous TREM2 c.549del; p.(Leu184Serfs*5) variant causing Nasu-Hakola disease in three siblings in a consanguineous Iraqi family: Case report and review of literature.

Molecular genetics &amp; genomic medicine
2024

TREM2 variants that cause early dementia and increase Alzheimer's disease risk affect gene splicing.

Brain : a journal of neurology
2023

Computational saturation mutagenesis to explore the effect of pathogenic mutations on extra-cellular domains of TREM2 associated with Alzheimer's and Nasu-Hakola disease.

Journal of molecular modeling
2023

A mild type of Nasu-Hakola disease - a case of a woman with presenile dementia and cystic bone lesions.

Archives of medical science : AMS
2023

Microglia and Brain Disorders: The Role of Vitamin D and Its Receptor.

International journal of molecular sciences
2023

Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation.

Acta neuropathologica
2023

A polarizing answer - microglia in Nasu-Hakola disease.

Nature immunology
2023

Nasu-Hakola Disease With Stroke-like Attack: A Case Report.

Alzheimer disease and associated disorders
2023

Human early-onset dementia caused by DAP12 deficiency reveals a unique signature of dysregulated microglia.

Nature immunology
2022

Lipomembranous fat necrosis: A distinctive and unique morphology (Review).

Experimental and therapeutic medicine
2022

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) positively regulates lipopolysaccharide-induced expression of CXC chemokine ligand 10 and 11 in mouse macrophages.

Biochemical and biophysical research communications
2022

Nasu-Hakola Disease - A Rare Type of Presenile Dementia.

Annals of Indian Academy of Neurology
2022

TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders.

Journal of Alzheimer's disease : JAD
2022

Primary Microglia Dysfunction or Microgliopathy: A Cause of Dementias and Other Neurological or Psychiatric Disorders.

Neuroscience
2022

The Primary Microglial Leukodystrophies: A Review.

International journal of molecular sciences
2022

Dynamic insights into the effects of nonsynonymous polymorphisms (nsSNPs) on loss of TREM2 function.

Scientific reports
2022

Advances in neuroRehabilitation of TREM2-related dementia: A case report on a novel multimodal approach using virtual reality.

Medicine
2022

Downregulation of m6A Methyltransferase in the Hippocampus of Tyrobp -/- Mice and Implications for Learning and Memory Deficits.

Frontiers in neuroscience
2022

Soluble TREM2: Innocent bystander or active player in neurological diseases?

Neurobiology of disease
2021

A Shotgun Proteomic Platform for a Global Mapping of Lymphoblastoid Cells to Gain Insight into Nasu-Hakola Disease.

International journal of molecular sciences
2021

Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke.

Scientific reports
2021

TREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features.

European journal of neurology
2021

Neuropathological Alzheimer's Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes.

Journal of Alzheimer's disease : JAD
2020

Reactive astrocytes express Aggregatin (FAM222A) in the brains of Alzheimer's disease and Nasu-Hakola disease.

Intractable &amp; rare diseases research
2020

Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice.

Molecular neurodegeneration
2020

Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from development to aging.

Neurochemistry international
2020

Differential regulation of TREM2 and CSF1R in CNS macrophages in an SIV/macaque model of HIV CNS disease.

Journal of neurovirology
2020

Mechanistic insights into the deleterious roles of Nasu-Hakola disease associated TREM2 variants.

Scientific reports
2019

Neurodegenerative Disease-Associated Variants in TREM2 Destabilize the Apical Ligand-Binding Region of the Immunoglobulin Domain.

Frontiers in neurology
2019

Microglia express TMEM119 in the brains of Nasu-Hakola disease.

Intractable &amp; rare diseases research
2019

Phenotypic Expansion in Nasu-Hakola Disease: Immunological Findings in Three Patients and Proposal of a Unifying Pathogenic Hypothesis.

Frontiers in immunology
2019

Microglia express GPNMB in the brains of Alzheimer's disease and Nasu-Hakola disease.

Intractable &amp; rare diseases research
2019

Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry.

JAMA network open
2020

A novel homozygous mutation in TREM2 found in a Chinese early-onset dementia family with mild bone involvement.

Neurobiology of aging
2019

Inflammatory expression profile in peripheral blood mononuclear cells from patients with Nasu-Hakola Disease.

Cytokine
2018

Microglia express gamma-interferon-inducible lysosomal thiol reductase in the brains of Alzheimer's disease and Nasu-Hakola disease.

Intractable &amp; rare diseases research
2019

Bone matrix hypermineralization associated with low bone turnover in a case of Nasu-Hakola disease.

Bone
2018

Early-onset dementia, leukoencephalopathy and brain calcifications: a clinical, imaging and pathological comparison of ALSP and PLOSL/Nasu Hakola disease.

Acta neurologica Belgica
2018

Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis.

Cell reports
2018

Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases.

Frontiers in cellular neuroscience
2018

Nasu Hakola Disease: A Rare Cause of Dementia and Cystic Bone Lesions, Report of a New Turkish Family.

Noro psikiyatri arsivi
2018

The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity.

Immunity
2018

Small nuclear RNA-mediated modulation of splicing reveals a therapeutic strategy for a TREM2 mutation and its post-transcriptional regulation.

Scientific reports
2018

Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia.

Stem cell reports
2018

Frontotemporal Dementia and Chorea Associated with a Compound Heterozygous TREM2 Mutation.

Journal of Alzheimer's disease : JAD
2018

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

Intractable &amp; rare diseases research
2018

Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy): First report from India.

Neurology India
2018

Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes.

International journal of molecular sciences
2017

Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.

Frontiers in molecular neuroscience
2017

Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease.

Intractable &amp; rare diseases research
2017

Evidence of CNS β-amyloid deposition in Nasu-Hakola disease due to the TREM2 Q33X mutation.

Neurology
2017

TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway.

Frontiers in aging neuroscience
2017

The Pathophysiological Role of Microglia in Dynamic Surveillance, Phagocytosis and Structural Remodeling of the Developing CNS.

Frontiers in molecular neuroscience
2017

OH MYeloid! Immune cells wreaking havoc on brain homeostasis.

The EMBO journal
2017

A split-luciferase complementation, real-time reporting assay enables monitoring of the disease-associated transmembrane protein TREM2 in live cells.

The Journal of biological chemistry
2017

TREM2, Microglia, and Neurodegenerative Diseases.

Trends in molecular medicine
2017

Expression of GPR17, a regulator of oligodendrocyte differentiation and maturation, in Nasu-Hakola disease brains.

Intractable &amp; rare diseases research
2017

A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature.

Neurobiology of aging
2016

The Alzheimer's Disease-Associated R47H Variant of TREM2 Has an Altered Glycosylation Pattern and Protein Stability.

Frontiers in neuroscience
2017

TREM2 Promotes Microglial Survival by Activating Wnt/β-Catenin Pathway.

The Journal of neuroscience : the official journal of the Society for Neuroscience
2016

Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms.

eLife
2016

Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains.

Intractable &amp; rare diseases research
2016

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

Intractable &amp; rare diseases research
2017

Microglia and brain macrophages: An update.

Neuropathology : official journal of the Japanese Society of Neuropathology
2017

Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

Brain pathology (Zurich, Switzerland)
2016

Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression.

Acta neuropathologica communications
2016

[Molecular Pathogenesis of Nasu-Hakola Disease Brain Lesions].

Brain and nerve = Shinkei kenkyu no shinpo
2016

Functional involvement of γ-secretase in signaling of the triggering receptor expressed on myeloid cells-2 (TREM2).

Journal of neuroinflammation
2016

Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone.

Multiple sclerosis (Houndmills, Basingstoke, England)
2016

Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status.

Acta neuropathologica
2016

The Triggering Receptor Expressed on Myeloid Cells 2: A Molecular Link of Neuroinflammation and Neurodegenerative Diseases.

The Journal of biological chemistry
2015

A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology
2016

Overexpression of TREM2 enhances glioma cell proliferation and invasion: a therapeutic target in human glioma.

Oncotarget
2015

The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective.

Research and reports in biochemistry
2015

The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E.

The Journal of biological chemistry
2015

TREM2 mRNA Expression in Leukocytes Is Increased in Alzheimer's Disease and Schizophrenia.

PloS one
2015

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

Neuropathology : official journal of the Japanese Society of Neuropathology
2015

Introducing directly induced microglia-like (iMG) cells from fresh human monocytes: a novel translational research tool for psychiatric disorders.

Frontiers in cellular neuroscience
2015

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

Neurogenetics
2015

TREM2 sustains microglial expansion during aging and response to demyelination.

The Journal of clinical investigation
2014

The Role of TREM2 in Alzheimer's Disease and Other Neurological Disorders.

Journal of Alzheimer's disease &amp; Parkinsonism
2015

Disease-Associated Mutations of TREM2 Alter the Processing of N-Linked Oligosaccharides in the Golgi Apparatus.

Traffic (Copenhagen, Denmark)
2014

A Comprehensive Profile of ChIP-Seq-Based PU.1/Spi1 Target Genes in Microglia.

Gene regulation and systems biology

Associações

Organizações que acompanham esta doença — pra ter apoio e orientação

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Comunidades

Grupos ativos de quem convive com esta doença aqui no Raras

Ainda não existe comunidade no Raras para Doença de Nasu-Hakola

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Doenças relacionadas

Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico

Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. A Novel Rare Homozygous R47C Variant in TREM2 with Frontal Variant Alzheimer's Disease.
    Neurology India· 2026· PMID 41817071mais citado
  2. System biology and network-based approach to identify the therapeutic signatures and potential inhibitors against polycystic lipomembranous osteodysplasia with Sclerosing Leukoencephalopathy.
    PloS one· 2026· PMID 41719345mais citado
  3. TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting.
    International journal of molecular sciences· 2025· PMID 40806186mais citado
  4. Neuroglia in leukodystrophies.
    Handbook of clinical neurology· 2025· PMID 40148043mais citado
  5. Generation of a human induced pluripotent stem cell line (BIHi292-A) from PBMCs of a female patient diagnosed with Nasu-Hakola disease (NHD)/polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) carrying a novel heterozygous mutation in the TREM2 gene.
    Stem cell research· 2025· PMID 39879812mais citado
  6. Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy.
    · 1993· PMID 20301376recente
  7. Nasu-Hakola Disease Presenting as Rapidly Progressive Dementia With Seizures: A TREM2 Mutation Case Without Skeletal Involvement.
    Cureus· 2025· PMID 41510405recente
  8. Roles of TREM2 in Alzheimer's disease.
    Transl Neurodegener· 2025· PMID 41168805recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:2770(Orphanet)
  2. MONDO:0009092(MONDO)
  3. GARD:9921(GARD (NIH))
  4. Variantes catalogadas(ClinVar)
  5. Busca completa no PubMed(PubMed)
  6. Q3281284(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar

Compêndio · Raras BR

Doença de Nasu-Hakola

ORPHA:2770 · MONDO:0009092
Prevalência
<1 / 1 000 000
Herança
Autosomal recessive
CID-10
G31.8 · Outras doenças degenerativas especificadas do sistema nervoso
CID-11
Início
Adolescent, Adult
Prevalência
0.0 (Europe)
MedGen
UMLS
C1857316
EuropePMC
Wikidata
Papers 10a
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