ADLD
MCID: LKD025
MIFTS: 36

Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant (ADLD)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

MalaCards integrated aliases for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

Name: Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant 58 74
Leukodystrophy, Adult-Onset, Autosomal Dominant 58 30 13 6 41
Adld 58 12 60 76
Adult-Onset Autosomal Dominant Demyelinating Leukodystrophy 12 60 15
Adult-Onset Autosomal Dominant Leukodystrophy 12 60 38
Pelizaeus-Merzbacher Disease, Autosomal Dominant or Late-Onset Type, Formerly 58
Autosomal-Dominant or Late-Onset Type Pelizaeus-Merzbacher Disease 12
Leukodystrophy, Demyelinating, Autosomal Dominant, Adult-Onset 76
Pelizaeus-Merzbacher Disease Autosomal Dominant 76
Adult Onset Autosomal Dominant Leukodystrophy 74
Pelizaeus-Merzbacher Disease Late-Onset Type 76
Multiple Sclerosis-Like Disorder 76

Characteristics:

Orphanet epidemiological data:

60
adult-onset autosomal dominant leukodystrophy
Inheritance: Autosomal dominant; Age of onset: Adult;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in the fourth to sixth decades (mean 40 years)
autonomic dysfunction usually precedes obvious neurologic deterioration
acute neurologic deterioration after viral illness has been reported
duplication of lmnb1 is sufficient for the disorder, although patients may also have larger duplications
one family with a deletion upstream of the lmnb1 gene did not have autonomic symptoms or cerebellar involvement


HPO:

33
leukodystrophy, demyelinating, adult-onset, autosomal dominant:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

OMIM : 58 Autosomal dominant adult-onset demyelinating leukodystrophy is a slowly progressive and fatal disorder that presents in the fourth or fifth decade of life and is characterized clinically by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. ADLD differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis (summary by Padiath et al., 2006). Characteristic MRI findings include T2-weighted hyperintense changes in the upper corticospinal tract and cerebellar peduncles, with later development of confluent white matter changes in the frontoparietal area with relative sparing of the periventricular white matter (summary by Schuster et al., 2011). (169500)

MalaCards based summary : Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant, also known as leukodystrophy, adult-onset, autosomal dominant, is related to autosomal dominant leukodystrophy with autonomic disease and leukodystrophy, and has symptoms including abnormal pyramidal signs, personality changes and cerebellar ataxia. An important gene associated with Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant is LMNB1 (Lamin B1). Affiliated tissues include spinal cord, eye and cerebellum, and related phenotypes are ataxia and nystagmus

Disease Ontology : 12 A leukodystrophy characterized by onset in the 4th or 5th decade of life of autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS that has material basis in heterozygous tandem genomic duplication resulting in an extra copy of the LMNB1 gene on chromosome 5q.

UniProtKB/Swiss-Prot : 76 Leukodystrophy, demyelinating, autosomal dominant, adult-onset: A slowly progressive and fatal demyelinating leukodystrophy, presenting in the fourth or fifth decade of life. Clinically characterized by early autonomic abnormalities, pyramidal and cerebellar dysfunction, and symmetric demyelination of the CNS. It differs from multiple sclerosis and other demyelinating disorders in that neuropathology shows preservation of oligodendroglia in the presence of subtotal demyelination and lack of astrogliosis.

Related Diseases for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Diseases related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autosomal dominant leukodystrophy with autonomic disease 11.7
2 leukodystrophy 10.3
3 rem sleep behavior disorder 10.2
4 multiple sclerosis 10.0
5 3-methylglutaconic aciduria, type iii 9.9
6 cerebral degeneration 9.6 HTRA1 LMNB1

Graphical network of the top 20 diseases related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:



Diseases related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Symptoms & Phenotypes for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Human phenotypes related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

60 33 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 60 33 hallmark (90%) Very frequent (99-80%) HP:0001251
2 nystagmus 60 33 frequent (33%) Frequent (79-30%) HP:0000639
3 spasticity 60 33 frequent (33%) Frequent (79-30%) HP:0001257
4 gait disturbance 60 33 frequent (33%) Frequent (79-30%) HP:0001288
5 tremor 60 33 frequent (33%) Frequent (79-30%) HP:0001337
6 hyperreflexia 60 33 frequent (33%) Frequent (79-30%) HP:0001347
7 constipation 60 33 frequent (33%) Frequent (79-30%) HP:0002019
8 hypotension 60 33 frequent (33%) Frequent (79-30%) HP:0002615
9 urinary urgency 60 33 frequent (33%) Frequent (79-30%) HP:0000012
10 impotence 60 33 frequent (33%) Frequent (79-30%) HP:0000802
11 tetraparesis 60 33 frequent (33%) Frequent (79-30%) HP:0002273
12 dilatation of the bladder 60 33 frequent (33%) Frequent (79-30%) HP:0010955
13 abnormal pyramidal sign 33 frequent (33%) HP:0007256
14 dysarthria 60 33 occasional (7.5%) Occasional (29-5%) HP:0001260
15 dysphagia 60 33 occasional (7.5%) Occasional (29-5%) HP:0002015
16 hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000365
17 global developmental delay 60 33 occasional (7.5%) Occasional (29-5%) HP:0001263
18 intellectual disability, mild 60 33 occasional (7.5%) Occasional (29-5%) HP:0001256
19 hypohidrosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000966
20 cerebral cortical atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0002120
21 visual loss 60 33 occasional (7.5%) Occasional (29-5%) HP:0000572
22 corpus callosum atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0007371
23 atrophy of the spinal cord 60 33 occasional (7.5%) Occasional (29-5%) HP:0006827
24 depressivity 33 HP:0000716
25 abnormal pyramidal signs 60 Frequent (79-30%)
26 babinski sign 33 HP:0003487
27 abnormality of the urinary system 33 HP:0000079
28 peripheral demyelination 33 HP:0011096
29 leukodystrophy 33 HP:0002415
30 orthostatic hypotension due to autonomic dysfunction 33 HP:0004926
31 personality changes 33 HP:0000751
32 gliosis 33 HP:0002171
33 abnormal autonomic nervous system physiology 33 HP:0012332
34 progressive neurologic deterioration 33 HP:0002344
35 pseudobulbar paralysis 33 HP:0007024
36 autonomic bladder dysfunction 33 HP:0005341
37 autonomic erectile dysfunction 33 HP:0008652
38 decreased sweating due to autonomic dysfunction 33 HP:0007480
39 abnormal cerebellum morphology 33 HP:0001317
40 diffuse leukoencephalopathy 33 HP:0006994
41 symmetric peripheral demyelination 33 HP:0007262

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus

Cardiovascular Vascular:
orthostatic hypotension due to autonomic dysfunction

Abdomen Gastrointestinal:
abnormal bowel regulation due to autonomic dysfunction

Genitourinary Bladder:
abnormal bladder regulation due to autonomic dysfunction

Laboratory Abnormalities:
patient cells have increased levels of lmnb1 mrna and protein

Neurologic Central Nervous System:
spasticity
hyperreflexia
autonomic dysfunction
pyramidal signs
extensor plantar responses
more
Neurologic Behavioral Psychiatric Manifestations:
personality changes
depression

Genitourinary External Genitalia Male:
impotence due to autonomic dysfunction

Skin Nails Hair Skin:
decreased sweating due to autonomic dysfunction

Clinical features from OMIM:

169500

UMLS symptoms related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:


abnormal pyramidal signs, personality changes, cerebellar ataxia, muscle spasticity, cerebellar signs

Drugs & Therapeutics for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Genetic Tests for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Genetic tests related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Leukodystrophy, Adult-Onset, Autosomal Dominant 30 LMNB1

Anatomical Context for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

MalaCards organs/tissues related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

42
Spinal Cord, Eye, Cerebellum, Parietal Lobe, Brain

Publications for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Articles related to Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

(show all 15)
# Title Authors Year
1
An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis. ( 28769756 )
2017
2
A longitudinal study of a family with adult-onset autosomal dominant leukodystrophy: Clinical, autonomic and neuropsychological findings. ( 26896090 )
2016
3
Brain magnetic resonance metabolic and microstructural changes in adult-onset autosomal dominant leukodystrophy. ( 26189928 )
2015
4
Adult-onset autosomal dominant leukodystrophy presenting with REM sleep behavior disorder. ( 23243074 )
2013
5
Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. ( 23681646 )
2013
6
Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. ( 23261988 )
2013
7
A^H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 23636437 )
2013
8
Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. ( 21909802 )
2012
9
Adult-onset autosomal dominant leukodystrophy: linking nuclear envelope to myelin. ( 21273400 )
2011
10
Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. ( 20719577 )
2011
11
Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. ( 21225301 )
2011
12
N-CAM dysfunction and unexpected accumulation of PSA-NCAM in brain of adult-onset autosomal-dominant leukodystrophy. ( 19725832 )
2010
13
MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 18945794 )
2009
14
MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. ( 16611789 )
2006
15
Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. ( 16823806 )
2006

Variations for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

ClinVar genetic disease variations for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 LMNB1 LMNB1, DUP, CHR5: 126,102,443-126,199,753 SRO, GRCh37 duplication Pathogenic

Expression for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Search GEO for disease gene expression data for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant.

Pathways for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

GO Terms for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

Sources for Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant

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