ADLD
MCID: ATS309
MIFTS: 23

Autosomal Dominant Leukodystrophy with Autonomic Disease (ADLD)

Categories: Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Autosomal Dominant Leukodystrophy with Autonomic Disease

MalaCards integrated aliases for Autosomal Dominant Leukodystrophy with Autonomic Disease:

Name: Autosomal Dominant Leukodystrophy with Autonomic Disease 24 53 25
Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy 24 53 25
Adld 24 53 25
Adult-Onset Autosomal Dominant Leukodystrophy with Autonomic Symptoms 24 25
Leukodystrophy, Demyelinating, Adult-Onset, Autosomal Dominant 53 72
Lmnb1-Related Adult-Onset Autosomal Dominant Leukodystrophy 24 25
Pelizaeus-Merzbacher Disease, Autosomal Dominant or Late-Onset Type 53
Adult-Onset Autosomal Dominant Demyelinating Leukodystrophy 53
Adult-Onset Autosomal Dominant Leukodystrophy 53
Adult Onset Autosomal Dominant Leukodystrophy 72
Multiple Sclerosis-Like Disorder 53

Characteristics:

GeneReviews:

24
Penetrance The disease presents in the fourth to fifth decades of adulthood with no gender variation. penetrance is not known but is thought to be 100%.

Classifications:



External Ids:

UMLS 72 C1868512 C3164344

Summaries for Autosomal Dominant Leukodystrophy with Autonomic Disease

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 99027DefinitionA rare, slowly progressive neurological disorder involving centralnervous systemdemyelination, leading to autonomic dysfunction, ataxia and mild cognitive impairment.EpidemiologyMore than 20 families in different ethnic groups have been reported to date. Exact prevalence and incidence data are however lacking.Clinical descriptionUnlike mostforms of leukodystrophy which appear in childhood, ADLD occurs in the 4th to 6th decade of life. ADLD may clinically resemble multiple sclerosis in the initial phase. In most patients, the initial manifestation of the disease is autonomic dysfunction resulting in micturitionurgency, bladder retention, constipation, postural hypotensionanderectile dysfunction in affected males. Decreased sweating is reported in some cases. Some patients develop autonomic dysfunction later in the disease course. The other features are cerebellardysfunction (gait ataxia, nystagmus, dysmetria, loss of fine motor control, and action tremors), pyramidal signs (spasticity, weakness of both upper and lower extremities, hyperreflexia), and cognitive impairment possibly with personality changes. These manifestations may not develop for years following initial presentation. Neuroradiologicalcharacteristics include extensive symmetrical white matter changes, corpus callosum atrophy, and brain stem and spinal cord atrophy. The disease follows a slow progressive course with an eventual loss of walking ability and slightly shortened lifespan.EtiologyADLD is caused by chromosomal rearrangements with duplications of the LMNB1 gene (5q23.2) or a ''position effect'' due to a genomic deletion upstream of the gene causing its upregulation. Overexpression of LMNB1 causes myelin disruptionin the central nervous system for which the precise underlying pathogenic mechanisms have not been elucidated. Alteration of splicing patterns suggests that ADLD is a spliceopathy.Genetic counselingGenetic counseling should be provided to affected families indicating the autosomal dominant pattern of inheritance.Visit the Orphanet disease page for more resources.

MalaCards based summary : Autosomal Dominant Leukodystrophy with Autonomic Disease, also known as autosomal dominant adult-onset demyelinating leukodystrophy, is related to demyelinating disease and pure autonomic failure, and has symptoms including personality changes, muscle spasticity and cerebellar ataxia. An important gene associated with Autosomal Dominant Leukodystrophy with Autonomic Disease is LMNB1 (Lamin B1). Affiliated tissues include spinal cord, brain and medulla oblongata.

Genetics Home Reference : 25 Autosomal dominant leukodystrophy with autonomic disease (ADLD) is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates and protects nerve fibers and promotes the rapid transmission of nerve impulses. People with ADLD develop signs and symptoms of the condition in adulthood, typically in their forties or fifties. The first signs of the condition often involve problems with the autonomic nervous system, which controls involuntary body processes such as the regulation of blood pressure and body temperature. These problems include difficulty with bowel and bladder function, a sharp drop in blood pressure upon standing (orthostatic hypotension), and erectile dysfunction in men. Rarely, people experience an inability to sweat (anhidrosis), which can lead to a dangerously high body temperature. In ADLD, movement difficulties often develop after the autonomic nervous system problems. Affected individuals can have muscle stiffness (spasticity) or weakness and involuntary rhythmic shaking, called intention tremor because it worsens during movement. People with ADLD often have difficulty coordinating movements (ataxia), including movements that involve judging distance or scale (dysmetria), such as picking up a distant object, and rapidly alternating movements (dysdiadochokinesis), including hand clapping or foot stomping. These movement problems usually first affect the legs, but as the condition worsens, the arms and eventually the face become involved. In some people with ADLD, the symptoms worsen during episodes of fever, infection, or exposure to heat. Due to difficulty walking and an unsteady gait, many affected individuals need a cane, walker, or wheelchair for assistance. Intelligence is usually unaffected; however, people who have had ADLD for a long time may have a decline in intellectual function (dementia). ADLD worsens slowly, and affected individuals usually survive 10 to 20 years after the onset of symptoms.

GeneReviews: NBK338165

Related Diseases for Autosomal Dominant Leukodystrophy with Autonomic Disease

Graphical network of the top 20 diseases related to Autosomal Dominant Leukodystrophy with Autonomic Disease:



Diseases related to Autosomal Dominant Leukodystrophy with Autonomic Disease

Symptoms & Phenotypes for Autosomal Dominant Leukodystrophy with Autonomic Disease

UMLS symptoms related to Autosomal Dominant Leukodystrophy with Autonomic Disease:


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

Drugs & Therapeutics for Autosomal Dominant Leukodystrophy with Autonomic Disease

Search Clinical Trials , NIH Clinical Center for Autosomal Dominant Leukodystrophy with Autonomic Disease

Genetic Tests for Autosomal Dominant Leukodystrophy with Autonomic Disease

Anatomical Context for Autosomal Dominant Leukodystrophy with Autonomic Disease

MalaCards organs/tissues related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

41
Spinal Cord, Brain, Medulla Oblongata

Publications for Autosomal Dominant Leukodystrophy with Autonomic Disease

Articles related to Autosomal Dominant Leukodystrophy with Autonomic Disease:

(show all 47)
# Title Authors PMID Year
1
A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD). 38 4
25701871 2015
2
LMNB1-related autosomal-dominant leukodystrophy: Clinical and radiological course. 4
26053668 2015
3
Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression. 4
26311780 2015
4
Messenger RNA processing is altered in autosomal dominant leukodystrophy. 4
25637521 2015
5
Consensus statement on preventive and symptomatic care of leukodystrophy patients. 4
25577286 2015
6
Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. 4
25987178 2015
7
Vitamin B12 deficiency: an important reversible co-morbidity in neuropsychiatric manifestations. 4
25722508 2015
8
Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts. 4
24858279 2014
9
Guidelines for the diagnosis and treatment of cobalamin and folate disorders. 4
24942828 2014
10
A practical approach to diagnosing adult onset leukodystrophies. 4
24357685 2014
11
Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype. 4
24262341 2014
12
Nuclear envelope: connecting structural genome organization to regulation of gene expression. 4
24563350 2014
13
Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant. 4
23681646 2013
14
Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression. 4
23649844 2013
15
Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model. 4
23676464 2013
16
Oct-1 recruitment to the nuclear envelope in adult-onset autosomal dominant leukodystrophy. 4
23261988 2013
17
Nuclear lamins in the brain - new insights into function and regulation. 4
23065386 2013
18
Nuclear lamin functions and disease. 4
22795640 2012
19
Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. 4
21909802 2012
20
Magnetic resonance imaging findings within the posterior and lateral columns of the spinal cord extended from the medulla oblongata to the thoracic spine in a woman with subacute combined degeneration without hematologic disorders: a case report and review of the literature. 4
21524288 2011
21
Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms. 4
21225301 2011
22
Isolated noradrenergic failure in adult-onset autosomal dominant leukodystrophy. 4
20719577 2011
23
A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations. 4
19961535 2010
24
Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and molecular case study of altered nuclear function and disease. 4
20816241 2010
25
A novel family with Lamin B1 duplication associated with adult-onset leucoencephalopathy. 4
19151023 2009
26
MR imaging characteristics and neuropathology of the spinal cord in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. 4
18945794 2009
27
A novel duplication confirms the involvement of 5q23.2 in autosomal dominant leukodystrophy. 4
19001169 2008
28
The earliest MR imaging and proton MR spectroscopy abnormalities in adult-onset Krabbe disease. 4
17824908 2007
29
Lamin B1 duplications cause autosomal dominant leukodystrophy. 4
16951681 2006
30
Adult-onset autosomal dominant leukodystrophy with autonomic symptoms restricted to 1.5 Mbp on chromosome 5q23. 4
16823806 2006
31
MR characteristics and neuropathology in adult-onset autosomal dominant leukodystrophy with autonomic symptoms. 4
16611789 2006
32
MR imaging and proton MR spectroscopy in adult Krabbe disease. 4
11003282 2000
33
Multiple sclerosis. 4
11006371 2000
34
MRI and CT in an autosomal-dominant, adult-onset leukodystrophy. 4
9225322 1997
35
Autosomal dominant late-onset leukoencephalopathy. Clinical report of a new Italian family. 4
9018034 1997
36
Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization. 4
8838815 1996
37
Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1. 4
8586436 1995
38
Structural organization of the human gene (LMNB1) encoding nuclear lamin B1. 4
7557986 1995
39
Clinical and pathological features of an autosomal dominant, adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. 4
8042923 1994
40
Computed tomography and magnetic resonance imaging in adult-onset leukodystrophy. 4
3415518 1988
41
Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis. 4
6472420 1984
42
New diagnostic criteria for multiple sclerosis: guidelines for research protocols. 4
6847134 1983
43
Allele-specific silencing as treatment for gene duplication disorders: proof-of-principle in autosomal dominant leukodystrophy. 38
31143934 2019
44
Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy. 38
30697589 2018
45
Adulthood leukodystrophies. 38
29302065 2018
46
An LMNB1 Duplication Caused Adult-Onset Autosomal Dominant Leukodystrophy in Chinese Family: Clinical Manifestations, Neuroradiology and Genetic Diagnosis. 38
28769756 2017
47
Autosomal Dominant Leukodystrophy with Autonomic Disease 38
26749591 2016

Variations for Autosomal Dominant Leukodystrophy with Autonomic Disease

Expression for Autosomal Dominant Leukodystrophy with Autonomic Disease

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GO Terms for Autosomal Dominant Leukodystrophy with Autonomic Disease

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