PLOSL1
MCID: PLY180
MIFTS: 56
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Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 (PLOSL1)
Categories:
Bone diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
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MalaCards integrated aliases for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:
Characteristics:Orphanet epidemiological data:58
nasu-hakola disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Finland); Age of onset: Adolescent,Adult; Age of death: adult; OMIM:56
Inheritance:
autosomal recessive
Miscellaneous:
profound dementia and death usually occurs by age 50 years HPO:31
polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1:
Inheritance autosomal recessive inheritance Classifications:
MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases Anatomical: Neuronal diseases Bone diseases Mental diseases
ICD10:
33
Orphanet: 58
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NIH Rare Diseases :
52
The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2770 Definition Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. Epidemiology Over 200 cases have been reported worldwide in the literature, the majority of them being in the Japanese and Finnish population. The prevalence in Finland is estimated between 1/500,000 and 1/1,000,000. Clinical description The disease course is generally divided into four stages: latent, osseous, early neurologic, and late neurologic. After a normal development during childhood (latent stage), the disease starts manifesting during adolescence or young adulthood (typical age of onset 20-30 years) with pain in the hands, wrists, ankles, and feet. Patients then start suffering from recurrent bone fractures due to polycystic osseous and osteoporotic lesions in the limb bones (osseous stage). During the third or fourth decade of life (early neurologic stage), patients present with pronounced personality changes (e.g. euphoria, lack of concentration, loss of judgment and social inhibitions) characteristic of a frontal lobe syndrome . Patients also typically suffer from initially mild, but progressive, memory disturbances. Epileptic seizures are frequently observed. Finally (late neurologic stage), patients progress to a profound dementia, are unable to speak and move, and usually die by the age of 50 years. Occasionally, the disease presents a different course with the neurologic symptoms preceding the osseous ones. Etiology NHD is due to mutations in either the TYROBP or TREM2 genes encoding the tyrosine kinase binding adaptor protein and the triggering receptor expressed on myeloid cells 2 respectively. These genes encode components of a signaling complex involved in the regulation of immune responses, the differentiation of dendritic cells and osteoclasts, and in the phagocytic activity of microglia. The exact pathogenic mechanism is unknown. Diagnostic methods Diagnosis is based on clinical and radiologic examination. X-ray imaging shows multifocal cystic lesions on the bones of hands, wrists, feet and ankles. Brain computed tomography (CT) or magnetic resonance imaging (MRI) shows frontally accentuated atrophy of the cerebral white matter. Bilateral calcifications of the basal ganglia are typical. EEG is normal in the early stages but shows diffuse slowing and irritative activity in late stages. Histopathologically, loss of axons and myelin as well as fibrillary gliosis are observed. Molecular genetic testing confirms the diagnosis in ambiguous cases. Differential diagnosis The combination of frontal-type dementia starting in the fourth decade and radiologically demonstrable polycystic osseous lesions is unique and facilitates the differentiation of NHD from other forms of familial and non-familial frontotemporal dementia such as frontotemporal dementia and parkinsonism linked to chromosome 17 (see this term). Antenatal diagnosis Due to the low carrier frequency of the mutation in the general population, prenatal diagnostic procedures are usually not reasonable, except in genetic isolates. Genetic counseling Transmission is autosomal recessive . Children of an NHD patient are healthy carriers of the mutation unless they have also inherited a disease-causing mutation in the TYROBP or TREM2 genes from the other parent. Presymptomatic testing is commercially available. Management and treatment There is no curative treatment for the disease. Management is supportive. Antiepileptic drugs are prescribed to prevent seizures. A regular orthopedic and neurologic surveillance is recommended. Prognosis NHD is a progressive disease that is fatal usually during the fifth decade of life. Visit the Orphanet disease page for more resources.
MalaCards based summary : Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1, also known as nasu-hakola disease, is related to dementia and solitary bone cyst, and has symptoms including seizures, myoclonus and personality changes. An important gene associated with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 is TYROBP (Transmembrane Immune Signaling Adaptor TYROBP), and among its related pathways/superpathways are Osteoclast differentiation and Innate Immune System. Affiliated tissues include bone, brain and myeloid, and related phenotypes are skeletal dysplasia and developmental regression Disease Ontology : 12 A syndrome that is characterized by progressive presenile dementia and recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities that has material basis in homozygous mutation in the TYRO protein tyrosine kinase binding protein (TYROBP) gene on chromosome 19q13 or homozygous mutation in the triggering receptor expressed on myeloid cells 2 (TREM2) gene on chromosome 6p21. Genetics Home Reference : 25 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain. "Polycystic lipomembranous osteodysplasia" refers to cyst-like bone changes that can be seen on x-rays. "Sclerosing leukoencephalopathy" describes specific changes in the brain that are found in people with this disorder. The bone abnormalities associated with PLOSL usually become apparent in a person's twenties. In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease. Several years later, broken bones (fractures) begin to occur frequently, particularly in bones of the ankles, feet, wrists, and hands. Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cyst-like changes. These abnormalities weaken bones and make them more likely to break. The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life. As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties. OMIM : 56 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is 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 usuallly leads to death in the fifth decade of life (summary by Kondo et al., 2002). (221770) KEGG : 36 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-hakola disease is an autosomal recessive inherited disorder. It is characterized by repeated fractures occurring during adolescence and progressive presenile dementia in the fourth decade. The disease is caused by a mutation in the TREM2 or DAP12 gene that regulates osteoclast differentiation. TREM2-DAP12 is also expressed by microglia, thus neurological impairments seen in this disease are considered to be directly caused by microglial dysfunstion. UniProtKB/Swiss-Prot : 73 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 usuallly leads to death in the fifth decade of life. Wikipedia : 74 Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease... more...
GeneReviews:
NBK1197
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Human phenotypes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:58 31 (show top 50) (show all 52)
Symptoms via clinical synopsis from OMIM:56Clinical features from OMIM:221770UMLS symptoms related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:seizures, myoclonus, personality changes, muscle spasticity, upper motor neuron signs MGI Mouse Phenotypes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:45
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Cochrane evidence based reviews: polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy |
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MalaCards organs/tissues related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:40
Bone,
Brain,
Myeloid,
Testes,
Monocytes,
Nk Cells,
Bone Marrow
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ClinVar genetic disease variations for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1:6 (show all 43)
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for disease gene expression data for Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1.
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Pathways related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to KEGG:36
Pathways related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:
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Cellular components related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:
Biological processes related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:(show all 25)
Molecular functions related to Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy 1 according to GeneCards Suite gene sharing:
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