Nasu-Hakola Disease
Latest Research
- A novel homozygous TREM2 c.257del variant in a Chinese family with Nasu-Hakola disease: A case study and literature review
Nasu-Hakola disease is a rare inherited condition that combines progressive dementia with bone cysts, usually caused by changes in the TREM2 or TYROBP genes. This report describes a middle-aged man from a related (consanguineous) Chinese family who developed early dementia and ankle pain; genetic testing revealed a previously unreported TREM2 mutation, and lab work showed it sharply lowers the TREM2 protein. The case widens the catalogue of disease-causing TREM2 changes and underscores how pairing brain and bone findings with genetic testing leads to the right diagnosis.
- A rare homozygous mutation in TYROBP resulting in early-onset dementia with bone cysts
Nasu-Hakola disease can be caused by faults in either of two genes, TREM2 or TYROBP. This report describes the first Chinese patient found to carry a TYROBP mutation, a 39-year-old with early-onset dementia and cystic bone lesions whose brain scan showed widespread atrophy and white-matter changes. Laboratory experiments suggested the variant disrupts how the TYROBP gene is processed. Detailed reports like this connect specific genetic changes to the disease and improve recognition of this easily-missed condition.
- Novel Compounds as TREM2 Modulators for Treating Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, and Nasu-Hakola Disease
Nasu-Hakola disease is caused by loss of the TREM2 receptor (or its partner TYROBP), so drugs that boost TREM2 activity are a leading therapeutic idea. This patent-style disclosure describes a new family of chemical compounds designed to modulate TREM2 and lists Nasu-Hakola disease among the conditions they might treat. It is very early-stage laboratory work, not a tested medicine, but it signals continued drug-discovery interest in the TREM2 pathway that is central to Nasu-Hakola, and is worth watching as candidates advance.
- Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy
GeneReviews is a trusted, expert-written and regularly updated clinical reference. This entry covers Nasu-Hakola disease (PLOSL) in depth: how it typically unfolds in four stages, from a silent early phase, to bone pain and fractures from cyst-like lesions in the third decade, to a frontal-lobe syndrome and progressive early dementia, and how it is diagnosed and managed. Written for clinicians and families, it is one of the most authoritative plain-language starting points for understanding this rare inherited brain-and-bone disease.
- System biology and network-based approach to identify therapeutic signatures and potential inhibitors against polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
There is no cure for Nasu-Hakola disease (also called PLOSL), and few treatment leads exist. Using computational "network biology," researchers analyzed gene-activity data to pinpoint the key genes and signaling hubs that appear to drive the disease, then searched for molecules that might block them. This is an early, computer-based step, not a tested treatment, but it highlights candidate targets and potential drug compounds that could guide future laboratory research toward therapies for this very rare disorder.
Archived · older than 6 months (6)
- Nasu-Hakola Disease Presenting as Rapidly Progressive Dementia With Seizures: A TREM2 Mutation Case Without Skeletal Involvement
Nasu-Hakola disease usually combines dementia with bone cysts, but it can present atypically. This case describes a patient with rapidly progressive dementia and seizures caused by a TREM2 mutation, but without the characteristic bone involvement. Recognizing that Nasu-Hakola can occur without the skeletal features matters, because doctors who expect the classic bone-and-brain combination might otherwise miss the diagnosis. Reports like this broaden awareness of how variably the disease can appear.
- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy: report of two cases
Nasu-Hakola disease (also called PLOSL) combines early dementia with bone changes and is easy to miss. This report describes two siblings who began having behavioral changes in their thirties and went on to develop similar cognitive decline, and walks through the steps that led to the genetic diagnosis. By documenting how the disease unfolded in one family and reviewing the medical literature, it helps doctors recognize this rare inherited condition sooner and gives families a clearer picture of its course.
- TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting
TREM2 is the gene most often behind Nasu-Hakola disease, and it also influences other brain disorders. This review catalogues the spectrum of TREM2 mutations, explains how the receptor normally helps microglia (the brain's immune cells) do their job, and surveys efforts to develop TREM2-targeted therapies. For Nasu-Hakola patients and families, it provides useful context on the gene at the heart of the disease and on the drug-development work aimed at it.
- Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease
When genetic testing finds a TREM2 change, doctors need to know whether it actually causes disease. TREM2 variants span a range, some cause Nasu-Hakola disease, others raise the risk of Alzheimer's or frontotemporal dementia, and most have unknown effects. This study examined dozens of TREM2 variants in the laboratory to sort out which ones harm the receptor's structure and function. Work like this improves the interpretation of genetic results, helping families receive clearer answers about TREM2-related conditions including Nasu-Hakola.
- Monoallelic TYROBP deletion is a novel risk factor for Alzheimer's disease
Nasu-Hakola disease occurs when someone inherits two faulty copies of TYROBP (or TREM2). This study focused on the TYROBP gene, including a large deletion that is a known cause of Nasu-Hakola in Finland, and asked what happens in people who carry just one faulty copy. Understanding how partial versus complete loss of TYROBP affects the brain sheds light on this gene's role in Nasu-Hakola and, more broadly, on how the same gene can produce very different outcomes depending on how much working protein remains.
- Generation of a human induced pluripotent stem cell line (BIHi292-A) from a patient with Nasu-Hakola disease (NHD)/PLOSL carrying a novel mutation in the TREM2 gene
Studying an ultra-rare disease like Nasu-Hakola is hard without good laboratory models. Researchers took blood cells from a woman with genetically confirmed Nasu-Hakola disease (PLOSL) carrying a new TREM2 mutation and reprogrammed them into induced pluripotent stem cells, a renewable cell line that can be grown into brain cells in the lab. This patient-derived resource gives scientists worldwide a realistic tool to investigate how the TREM2 mutation causes disease and to test potential treatments.
New & Recruiting Trials
- RecruitingLongitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases
This Italian natural-history study follows adults with ultra-rare inherited metabolic and degenerative neurological diseases (those affecting fewer than 5 in 100,000 people), a category that includes Nasu-Hakola disease (PLOSL). Researchers systematically gather clinical, laboratory and imaging data over time to understand how these conditions progress. It is observational, with no treatment involved, and open to adults aged 18 and older. Taking part can help expand what is known about this very rare bone-and-brain disorder; discuss whether it suits you with your care team.
These links to external research and clinical-trial listings are provided for information only and are not medical advice. Always discuss any study, treatment, or trial with your own doctor. Listings are gathered automatically from PubMed/Europe PMC and ClinicalTrials.gov and reviewed for relevance.