MCID: LKN019
MIFTS: 36

Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Mental diseases

Aliases & Classifications for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

MalaCards integrated aliases for Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

Name: Leukoencephalopathy, Diffuse Hereditary, with Spheroids 54 50 71
Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia 23 50 25 56
Hereditary Diffuse Leukoencephalopathy with Spheroids 50 56 29 69
Alsp 23 25 56 71
Autosomal Dominant Leukoencephalopathy with Neuroaxonal Spheroids 50 56 71
Hdls 50 56 71
Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids and Pigmented Glia 25 56
Pigmentary Orthochromatic Leukodystrophy 50 56
Familial Progressive Subcortical Gliosis 56 71
Subcortical Gliosis of Neumann 56 71
Gliosis 42 69
Pold 50 56
Gpsc 56 71
Leukoencephalopathy, Adult-Onset, with Axonal Spheroids and Pigmented Glia 71
Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids 50
Adult-Onset Leukodystrophy with Neuroaxonal Spheroids 50
Gliosis, Familial Progressive Subcortical 13
Familial Dementia, Neumann Type 56
Familial Dementia Neumann Type 71
Neuroaxonal Leukodystrophy 50
Fpsg 56

Characteristics:

Orphanet epidemiological data:

56
hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult; Age of death: adult;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
rapidly progressive
adult onset
variable presentation and evolution of symptoms
death within 6 years after onset


HPO:

32
leukoencephalopathy, diffuse hereditary, with spheroids:
Onset and clinical course rapidly progressive adult onset
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Penetrance appears to be incomplete [karle et al 2013, sundal et al 2015]; however, estimates have not been calculated given the limited number of families reported to date. although alsp is a dominantly inherited disease, de novo mutation occurs and variable expressivity in terms of the phenotype and the disease course can be found in members of the same family sharing the same pathogenic variant...

Classifications:

Orphanet: 56  
Rare neurological diseases


Summaries for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Genetics Home Reference : 25 Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells (neurons) and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI). Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.

MalaCards based summary : Leukoencephalopathy, Diffuse Hereditary, with Spheroids, also known as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, is related to csf1r-related hereditary diffuse leukoencephalopathy with spheroids and hypoalphalipoproteinemia, and has symptoms including hyperreflexia, spasticity and bradykinesia. An important gene associated with Leukoencephalopathy, Diffuse Hereditary, with Spheroids is CSF1R (Colony Stimulating Factor 1 Receptor). Affiliated tissues include brain and parietal lobe.

NIH Rare Diseases : 50 hereditary diffuse leukoencephalopathy with spheroids (hdls) is a neurological condition characterized by changes to certain areas of the brain. a hallmark of hdls is leukoencephalopathy, which is damage to a type of brain tissue called white matter. another common finding is axon damage due to swellings called spheroids. damage to myelin and axons is thought to contribute to many of the neurological signs and symptoms seen in people with this condition, including the personality changes, loss of memory, changes in motor skills and dementia. hdls is caused by mutations in the csf1r gene. it is inherited in an autosomal dominant pattern. last updated: 3/27/2013

UniProtKB/Swiss-Prot : 71 Leukoencephalopathy, diffuse hereditary, with spheroids: An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.

OMIM : 54
Hereditary diffuse leukoencephalopathy with spheroids is an autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes (summary by Rademakers et al., 2012). (221820)

Wikipedia : 72 Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare adult onset autosomal dominant... more...

GeneReviews: NBK100239

Related Diseases for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Diseases in the Leukoencephalopathy, Diffuse Hereditary, with Spheroids family:

Csf1r-Related Hereditary Diffuse Leukoencephalopathy with Spheroids

Diseases related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
id Related Disease Score Top Affiliating Genes
1 csf1r-related hereditary diffuse leukoencephalopathy with spheroids 12.4
2 hypoalphalipoproteinemia 12.0
3 tangier disease 11.9
4 hyperalphalipoproteinemia 11.2
5 hepatic lipase deficiency 11.2
6 huntington disease-like syndrome 10.9
7 symmetrical thalamic calcifications 10.8
8 apolipoprotein c-iii deficiency 10.8
9 hypobetalipoproteinemia, familial, 2 10.8
10 analbuminemia 10.8
11 chylomicron retention disease 10.8
12 glutaricaciduria, type i 10.8
13 hyperchylomicronemia, late-onset 10.7
14 norum disease 10.7
15 prediabetes syndrome 10.7
16 fish-eye disease 10.7
17 hypobetalipoproteinemia 10.7
18 supranuclear palsy, progressive 10.7
19 leigh syndrome 10.7
20 creutzfeldt-jakob disease 10.7
21 leukodystrophy 10.4
22 hepatitis 10.4
23 atherosclerosis 10.4
24 heart disease 10.3
25 endotheliitis 10.3
26 artery disease 10.3
27 coronary artery disease 10.3
28 obesity 10.2
29 dementia 10.2
30 nasu-hakola disease 10.2
31 hypertriglyceridemia 10.1
32 myocardial infarction 10.1
33 ischemic heart disease 10.0
34 spastic hemiplegia 9.9
35 hemiplegia 9.9
36 spasticity 9.9
37 primary progressive multiple sclerosis 9.9
38 prostatitis 9.8
39 hyperglycemia 9.8
40 acute myocardial infarction 9.8
41 prostate cancer 9.7
42 vascular disease 9.7
43 kidney disease 9.7

Graphical network of the top 20 diseases related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids:



Diseases related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Symptoms & Phenotypes for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hyperreflexia
spasticity
memory loss
bradykinesia
rigidity
more
Neurologic- Behavioral Psychiatric Manifestations:
depression
executive dysfunction
flat affect
behavioral changes


Clinical features from OMIM:

221820

Human phenotypes related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

32 (show all 16)
id Description HPO Frequency HPO Source Accession
1 hyperreflexia 32 HP:0001347
2 spasticity 32 HP:0001257
3 bradykinesia 32 HP:0002067
4 rigidity 32 HP:0002063
5 shuffling gait 32 HP:0002362
6 postural instability 32 HP:0002172
7 depression 32 HP:0000716
8 memory impairment 32 HP:0002354
9 leukoencephalopathy 32 HP:0002352
10 gliosis 32 HP:0002171
11 mutism 32 HP:0002300
12 apraxia 32 HP:0002186
13 frontal lobe dementia 32 HP:0000727
14 neuronal loss in central nervous system 32 HP:0002529
15 abnormality of the cerebral white matter 32 HP:0002500
16 cns demyelination 32 HP:0007305

UMLS symptoms related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids:


hemiplegia, polydipsia, muscle weakness, muscle rigidity, muscle spasticity, bradykinesia, memory loss

Drugs & Therapeutics for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Search Clinical Trials , NIH Clinical Center for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Cochrane evidence based reviews: gliosis

Genetic Tests for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Genetic tests related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

id Genetic test Affiliating Genes
1 Hereditary Diffuse Leukoencephalopathy with Spheroids 29

Anatomical Context for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

MalaCards organs/tissues related to Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

39
Brain, Parietal Lobe

Publications for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Variations for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

UniProtKB/Swiss-Prot genetic disease variations for Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

71 (show all 14)
id Symbol AA change Variation ID SNP ID
1 CSF1R p.Gly589Glu VAR_067397 rs281860268
2 CSF1R p.Glu633Lys VAR_067398 rs281860269
3 CSF1R p.Met766Thr VAR_067401 rs281860270
4 CSF1R p.Ala770Pro VAR_067402 rs281860271
5 CSF1R p.Ile775Asn VAR_067404 rs281860273
6 CSF1R p.Ile794Thr VAR_067405 rs281860274
7 CSF1R p.Asp837Tyr VAR_067406 rs387906662
8 CSF1R p.Phe849Ser VAR_067407 rs281860277
9 CSF1R p.Leu868Pro VAR_067409 rs281860278
10 CSF1R p.Met875Thr VAR_067410 rs281860279
11 CSF1R p.Pro878Thr VAR_067411 rs281860280
12 CSF1R p.Cys653Arg VAR_072081 rs690016559
13 CSF1R p.Ile843Phe VAR_072082 rs690016558
14 CSF1R p.Ile906Thr VAR_072083 rs690016560

ClinVar genetic disease variations for Leukoencephalopathy, Diffuse Hereditary, with Spheroids:

6 (show all 44)
id Gene Variation Type Significance SNP ID Assembly Location
1 CSF1R NM_005211.3(CSF1R): c.2624T> C (p.Met875Thr) single nucleotide variant Pathogenic rs281860279 GRCh37 Chromosome 5, 149434830: 149434830
2 CSF1R NM_005211.3(CSF1R): c.1897G> A (p.Glu633Lys) single nucleotide variant Pathogenic rs281860269 GRCh37 Chromosome 5, 149440497: 149440497
3 CSF1R NM_005211.3(CSF1R): c.1754-2A> G single nucleotide variant Pathogenic rs281860267 GRCh37 Chromosome 5, 149441160: 149441160
4 CSF1R NM_005211.3(CSF1R): c.2381T> C (p.Ile794Thr) single nucleotide variant Pathogenic rs281860274 GRCh37 Chromosome 5, 149435843: 149435843
5 CSF1R NM_005211.3(CSF1R): c.2509G> T (p.Asp837Tyr) single nucleotide variant Pathogenic rs387906662 GRCh37 Chromosome 5, 149435634: 149435634
6 CSF1R NM_005211.3(CSF1R): c.1766G> A (p.Gly589Glu) single nucleotide variant Pathogenic rs281860268 GRCh37 Chromosome 5, 149441146: 149441146
7 CSF1R NM_005211.3(CSF1R): c.2297T> C (p.Met766Thr) single nucleotide variant Pathogenic rs281860270 GRCh37 Chromosome 5, 149436872: 149436872
8 CSF1R NM_005211.3(CSF1R): c.2308G> C (p.Ala770Pro) single nucleotide variant Pathogenic rs281860271 GRCh37 Chromosome 5, 149436861: 149436861
9 CSF1R NM_005211.3(CSF1R): c.2320-2A> G single nucleotide variant Pathogenic rs281860272 GRCh37 Chromosome 5, 149435906: 149435906
10 CSF1R NM_005211.3(CSF1R): c.2324T> A (p.Ile775Asn) single nucleotide variant Pathogenic rs281860273 GRCh37 Chromosome 5, 149435900: 149435900
11 CSF1R NM_005211.3(CSF1R): c.2345G> A (p.Arg782His) single nucleotide variant Pathogenic rs281860281 GRCh37 Chromosome 5, 149435879: 149435879
12 CSF1R NM_005211.3(CSF1R): c.2442+5G> C single nucleotide variant Pathogenic rs281860275 GRCh37 Chromosome 5, 149435777: 149435777
13 CSF1R NM_005211.3(CSF1R): c.2546T> C (p.Phe849Ser) single nucleotide variant Pathogenic rs281860277 GRCh37 Chromosome 5, 149435597: 149435597
14 CSF1R NM_005211.3(CSF1R): c.2546_2548delTCT (p.Phe849del) deletion Pathogenic rs281860276 GRCh37 Chromosome 5, 149435595: 149435597
15 CSF1R NM_005211.3(CSF1R): c.2603T> C (p.Leu868Pro) single nucleotide variant Pathogenic rs281860278 GRCh37 Chromosome 5, 149434851: 149434851
16 CSF1R NM_005211.3(CSF1R): c.2632C> A (p.Pro878Thr) single nucleotide variant Pathogenic rs281860280 GRCh37 Chromosome 5, 149434822: 149434822
17 CSF1R NM_005211.3(CSF1R): c.1958G> A (p.Cys653Tyr) single nucleotide variant Pathogenic rs397515555 GRCh37 Chromosome 5, 149440436: 149440436
18 CSF1R NM_005211.3(CSF1R): c.2329C> T (p.Arg777Trp) single nucleotide variant Pathogenic rs397515556 GRCh37 Chromosome 5, 149435895: 149435895
19 CSF1R NM_005211.3(CSF1R): c.2483T> C (p.Phe828Ser) single nucleotide variant Pathogenic rs397515557 GRCh37 Chromosome 5, 149435660: 149435660
20 CSF1R NM_005211.3(CSF1R): c.2060_2061insT (p.Ser688Glufs) insertion Pathogenic rs587777245 GRCh38 Chromosome 5, 150059772: 150059772
21 CSF1R NM_005211.3(CSF1R): c.2442+1G> T single nucleotide variant Pathogenic rs587777246 GRCh38 Chromosome 5, 150056218: 150056218
22 CSF1R NM_005211.3(CSF1R): c.2342C> A (p.Ala781Glu) single nucleotide variant Pathogenic rs587777247 GRCh38 Chromosome 5, 150056319: 150056319
23 CSF1R NM_005211.3(CSF1R): c.2717T> C (p.Ile906Thr) single nucleotide variant Pathogenic rs690016560 GRCh38 Chromosome 5, 150054368: 150054368
24 CSF1R NM_005211.3(CSF1R): c.2701C> T (p.Pro901Ser) single nucleotide variant Pathogenic rs690016553 GRCh38 Chromosome 5, 150054384: 150054384
25 CSF1R NM_005211.3(CSF1R): c.2655-2A> G single nucleotide variant Pathogenic rs690016554 GRCh38 Chromosome 5, 150054432: 150054432
26 CSF1R NM_005211.3(CSF1R): c.2629C> T (p.Gln877Ter) single nucleotide variant Pathogenic rs690016556 GRCh38 Chromosome 5, 150055262: 150055262
27 CSF1R NM_005211.3(CSF1R): c.2566T> C (p.Tyr856His) single nucleotide variant Pathogenic rs690016552 GRCh38 Chromosome 5, 150055325: 150055325
28 CSF1R NM_005211.3(CSF1R): c.2562T> A (p.Asn854Lys) single nucleotide variant Pathogenic rs690016565 GRCh38 Chromosome 5, 150055329: 150055329
29 CSF1R NM_005211.3(CSF1R): c.2541G> C (p.Glu847Asp) single nucleotide variant Pathogenic rs690016551 GRCh38 Chromosome 5, 150056039: 150056039
30 CSF1R NM_005211.3(CSF1R): c.2528T> A (p.Ile843Asn) single nucleotide variant Pathogenic rs690016555 GRCh38 Chromosome 5, 150056052: 150056052
31 CSF1R NM_005211.3(CSF1R): c.2527A> T (p.Ile843Phe) single nucleotide variant Pathogenic rs690016558 GRCh38 Chromosome 5, 150056053: 150056053
32 CSF1R NM_005211.3(CSF1R): c.2512G> C (p.Val838Leu) single nucleotide variant Pathogenic rs690016557 GRCh38 Chromosome 5, 150056068: 150056068
33 CSF1R NM_005211.3(CSF1R): c.2480T> C (p.Ile827Thr) single nucleotide variant Pathogenic rs690016550 GRCh38 Chromosome 5, 150056100: 150056100
34 CSF1R NM_005211.3: c.2467C> T single nucleotide variant Pathogenic rs690016562 GRCh38 Chromosome 5, 150056112: 150056112
35 CSF1R NM_005211.3(CSF1R): c.2450T> C (p.Leu817Pro) single nucleotide variant Pathogenic rs690016549 GRCh38 Chromosome 5, 150056130: 150056130
36 CSF1R NM_005211.3(CSF1R): c.2378A> C (p.Lys793Thr) single nucleotide variant Pathogenic rs690016561 GRCh38 Chromosome 5, 150056283: 150056283
37 CSF1R NM_005211.3(CSF1R): c.2350G> A (p.Val784Met) single nucleotide variant Pathogenic rs690016564 GRCh38 Chromosome 5, 150056311: 150056311
38 CSF1R NM_005211.3(CSF1R): c.2342C> T (p.Ala781Val) single nucleotide variant Pathogenic rs587777247 GRCh38 Chromosome 5, 150056319: 150056319
39 CSF1R NM_005211.3(CSF1R): c.2330G> A (p.Arg777Gln) single nucleotide variant Pathogenic rs690016548 GRCh38 Chromosome 5, 150056331: 150056331
40 CSF1R NM_005211.3(CSF1R): c.2294G> A (p.Gly765Asp) single nucleotide variant Pathogenic rs690016566 GRCh38 Chromosome 5, 150057312: 150057312
41 CSF1R NM_005211.3(CSF1R): c.1957T> C (p.Cys653Arg) single nucleotide variant Pathogenic rs690016559 GRCh38 Chromosome 5, 150060874: 150060874
42 CSF1R NM_005211.3(CSF1R): c.1889T> G (p.Leu630Arg) single nucleotide variant Pathogenic rs690016547 GRCh38 Chromosome 5, 150060942: 150060942
43 CSF1R NM_005211.3(CSF1R): c.1745T> C (p.Leu582Pro) single nucleotide variant Pathogenic rs690016563 GRCh38 Chromosome 5, 150061731: 150061731
44 CSF1R NM_005211.3(CSF1R): c.1699delA (p.Thr567Argfs) deletion Pathogenic rs690016546 GRCh38 Chromosome 5, 150061777: 150061777

Expression for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

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Pathways for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

GO Terms for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

Sources for Leukoencephalopathy, Diffuse Hereditary, with Spheroids

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