PLSA1
MCID: PRM092
MIFTS: 48

Primary Lateral Sclerosis, Adult, 1 (PLSA1)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Primary Lateral Sclerosis, Adult, 1

MalaCards integrated aliases for Primary Lateral Sclerosis, Adult, 1:

Name: Primary Lateral Sclerosis, Adult, 1 58 13 74
Adult-Onset Primary Lateral Sclerosis 60
Primary Lateral Sclerosis 60
Lateral Sclerosis 74
Pls, Adult; Plsa 58
Adult-Onset Pls 60
Pls, Adult 58
Plsa1 58
Plsa 58
Pls 60

Characteristics:

Orphanet epidemiological data:

60
primary lateral sclerosis
Inheritance: Autosomal recessive,Not applicable; Prevalence: 1-9/100000 (Europe); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
average age at onset between 40 and 50 years


HPO:

33
primary lateral sclerosis, adult, 1:
Onset and clinical course adult onset slow progression
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


External Ids:

OMIM 58 611637
ICD10 via Orphanet 35 G12.2
UMLS via Orphanet 75 C0154682 C1968845
Orphanet 60 ORPHA35689
MedGen 43 C1968845

Summaries for Primary Lateral Sclerosis, Adult, 1

NINDS : 55 Primary lateral sclerosis (PLS) is a rare neuromuscular disease with slowly progressive weakness in voluntary muscle movement. PLS belongs to a group of disorders known as motor neuron diseases. PLS affects the upper motor neurons (also called corticospinal neurons) in the arms, legs, and face.  It occurs when nerve cells in the motor regions of the cerebral cortex (the thin layer of cells covering the brain which is responsible for most higher level mental functions) gradually degenerate, causing movements to be slow and effortful.  The disorder often affects the legs first, followed by the body, trunk, arms and hands, and, finally the bulbar muscles (muscles that control speech, swallowing, and chewing).  Symptoms include weakness, muscle stiffness and spasticity, clumsiness, slowing of movement, and problems with balance and speech. PLS is more common in men than in women, with a varied gradual onset that generally occurs between ages 40 and 60. PLS progresses gradually over a number of years, or even decades. Scientists do not believe PLS has a simple hereditary cause.  The diagnosis of PLS requires extensive testing to exclude other diseases. When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia.  Most neurologists follow an affected individual's clinical course for at least 3 to 4 years before making a diagnosis of PLS.

MalaCards based summary : Primary Lateral Sclerosis, Adult, 1, also known as adult-onset primary lateral sclerosis, is related to spasticity and spastic paraparesis, and has symptoms including upper motor neuron signs An important gene associated with Primary Lateral Sclerosis, Adult, 1 is SPG7 (SPG7 Matrix AAA Peptidase Subunit, Paraplegin), and among its related pathways/superpathways are Neuroscience and Copper homeostasis. The drugs Levetiracetam and Anticonvulsants have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and cortex, and related phenotypes are babinski sign and abnormal upper motor neuron morphology

OMIM : 58 Although primary lateral sclerosis (PLS) is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria were established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352). (611637)

Wikipedia : 77 Primary lateral sclerosis (PLS) is a rare neuromuscular disease characterized by progressive muscle... more...

Related Diseases for Primary Lateral Sclerosis, Adult, 1

Diseases in the Lateral Sclerosis family:

Primary Lateral Sclerosis, Juvenile Primary Lateral Sclerosis, Adult, 1

Diseases related to Primary Lateral Sclerosis, Adult, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 152)
# Related Disease Score Top Affiliating Genes
1 spasticity 30.2 SPAST SPG7
2 spastic paraparesis 30.0 SPAST SPG7
3 hereditary spastic paraplegia 30.0 ALS2 SPAST SPG7
4 supranuclear palsy, progressive, 1 29.8 MAPT SNCA
5 aphasia 29.5 MAPT SNCA
6 amyotrophic lateral sclerosis 1 29.2 ALS2 MAPT SNCA SOD1 SPAST
7 frontotemporal dementia 29.0 MAPT SNCA SOD1
8 motor neuron disease 28.2 ALS2 ARHGEF2 MAPT SNCA SOD1
9 papillon-lefevre syndrome 12.2
10 platelet groups--pl system 12.1
11 lateral sclerosis 12.1
12 primary lateral sclerosis, juvenile 11.9
13 pityriasis lichenoides 11.4
14 pleomorphic liposarcoma 11.4
15 pancreatic lipase deficiency 11.2
16 haim-munk syndrome 11.2
17 juvenile spinal muscular atrophy 11.1
18 progressive muscular atrophy 11.1
19 proximal spinal muscular atrophy 11.1
20 potocki-lupski syndrome 11.1
21 xanthomatosis 11.0
22 enthesopathy 11.0
23 skin tag 11.0
24 proteus-like syndrome 11.0
25 myocardial infarction 10.3
26 allergic encephalomyelitis 10.2
27 polydactyly 10.2
28 spastic paraplegia 4, autosomal dominant 10.1 SPAST SPG7
29 ornithosis 10.1
30 amyotrophic lateral sclerosis 16, juvenile 10.1 ALS2 SOD1
31 paraplegia 10.1
32 amyotrophic lateral sclerosis 2, juvenile 10.1 ALS2 SOD1
33 acute myocardial infarction 10.1
34 leukemia 10.1
35 brown-vialetto-van laere syndrome 10.1 ALS2 SOD1
36 intermittent claudication 10.1
37 blood group, junior system 10.0
38 lymphogranuloma venereum 10.0
39 spondyloenchondrodysplasia 10.0
40 cardiogenic shock 10.0
41 spastic paraplegia 7, autosomal recessive 10.0
42 cutis laxa, autosomal dominant 1 10.0 SNCA SOD1
43 arteries, anomalies of 9.9
44 prostate cancer 9.9
45 rheumatoid arthritis 9.9
46 tetralogy of fallot 9.9
47 prostate cancer, hereditary, 8 9.9
48 prostate cancer, hereditary, 6 9.9
49 blood group, gerbich system 9.9
50 acute leukemia 9.9

Comorbidity relations with Primary Lateral Sclerosis, Adult, 1 via Phenotypic Disease Network (PDN):


Acute Cystitis Intermittent Claudication

Graphical network of the top 20 diseases related to Primary Lateral Sclerosis, Adult, 1:



Diseases related to Primary Lateral Sclerosis, Adult, 1

Symptoms & Phenotypes for Primary Lateral Sclerosis, Adult, 1

Human phenotypes related to Primary Lateral Sclerosis, Adult, 1:

60 33 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 babinski sign 60 33 hallmark (90%) Very frequent (99-80%) HP:0003487
2 abnormal upper motor neuron morphology 60 33 hallmark (90%) Very frequent (99-80%) HP:0002127
3 generalized hyperreflexia 60 33 hallmark (90%) Very frequent (99-80%) HP:0007034
4 dysphagia 60 33 frequent (33%) Frequent (79-30%) HP:0002015
5 spastic gait 60 33 frequent (33%) Frequent (79-30%) HP:0002064
6 progressive spastic paraparesis 60 33 frequent (33%) Frequent (79-30%) HP:0007199
7 pseudobulbar signs 60 33 frequent (33%) Frequent (79-30%) HP:0002200
8 loss of speech 60 33 frequent (33%) Frequent (79-30%) HP:0002371
9 spastic dysarthria 60 33 frequent (33%) Frequent (79-30%) HP:0002464
10 emg: chronic denervation signs 60 33 frequent (33%) Frequent (79-30%) HP:0003444
11 cervical spinal cord atrophy 60 33 occasional (7.5%) Occasional (29-5%) HP:0010873
12 motor axonal neuropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0007002
13 spasticity 60 Very frequent (99-80%)
14 hyperreflexia 33 HP:0001347
15 spastic tetraparesis 33 HP:0001285
16 sensory impairment 60 Excluded (0%)
17 upper motor neuron dysfunction 60 Very frequent (99-80%)
18 atrophy of the spinal cord 60 Occasional (29-5%)
19 abnormal lower motor neuron morphology 60 Excluded (0%)
20 weakness due to upper motor neuron dysfunction 60 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
hyperreflexia
spastic gait
spastic tetraparesis
spastic dysarthria
upper motor neuron signs
more
Neurologic Peripheral Nervous System:
no sensory abnormalities

Abdomen Gastrointestinal:
dysphagia

Clinical features from OMIM:

611637

UMLS symptoms related to Primary Lateral Sclerosis, Adult, 1:


upper motor neuron signs

MGI Mouse Phenotypes related to Primary Lateral Sclerosis, Adult, 1:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.43 ALS2 MAPT SNCA SOD1 SPAST SPG7
2 nervous system MP:0003631 9.17 ALS2 ARHGEF2 MAPT SNCA SOD1 SPAST

Drugs & Therapeutics for Primary Lateral Sclerosis, Adult, 1

Drugs for Primary Lateral Sclerosis, Adult, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 23)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Levetiracetam Approved, Investigational Phase 2 102767-28-2 441341
2 Anticonvulsants Phase 2
3 Nootropic Agents Phase 2
4
4-Aminopyridine Approved Phase 1 504-24-5 1727
5
Carbidopa Approved Phase 1 28860-95-9 34359
6
Benzocaine Approved, Investigational Phase 1 1994-09-7, 94-09-7 2337
7
Levodopa Approved Phase 1 59-92-7 6047
8
Dopamine Approved Phase 1 62-31-7, 51-61-6 681
9
tannic acid Approved Phase 1 1401-55-4
10 Potassium Channel Blockers Phase 1
11 Aromatic Amino Acid Decarboxylase Inhibitors Phase 1
12 Dopamine Agents Phase 1
13 Adjuvants, Immunologic Phase 1
14 Immunologic Factors Phase 1
15 Antiparkinson Agents Phase 1
16 Carbidopa, levodopa drug combination Phase 1
17 Neurotransmitter Agents Phase 1
18 Dopamine agonists Phase 1
19
Coal tar Approved 8007-45-2
20
Choline Approved, Nutraceutical 62-49-7 305
21
Creatine Approved, Investigational, Nutraceutical 57-00-1 586
22 Aspartic Acid
23 N-Methylaspartate

Interventional clinical trials:

(show all 23)
# Name Status NCT ID Phase Drugs
1 Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease Completed NCT00324454 Phase 2
2 Autologous Bone Marrow-Derived Stem Cell Therapy for Motor Neuron Disease Active, not recruiting NCT03067857 Phase 1, Phase 2
3 A Study to Assess FLX-787 in Subjects With Motor Neuron Disease Experiencing Muscle Cramps. Terminated NCT03196375 Phase 2 FLX-787-ODT (orally disintegrating tablet);Placebo ODT
4 Use of Dalfampridin in Primary Lateral Sclerosis Recruiting NCT02868567 Phase 1 dalfampridine
5 Sinemet for Spasticity and Function in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis Enrolling by invitation NCT03929068 Phase 1 carbidopa-levodopa;Placebo Oral Tablet
6 Screening and Natural History: Primary Lateral Sclerosis and Related Disorders Completed NCT00015444
7 Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis Completed NCT00023075
8 Brain Function in Primary Lateral Sclerosis Completed NCT00071435
9 Brain Function in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis Completed NCT00334516
10 Oxidative Stress in Motor Neuron Disease: COSMOS Add-On Study Completed NCT01143428
11 Muscle Ultrasound Measures as Biomarkers of Upper Motor Neuron Function Completed NCT02408900
12 Collection of Blood Samples for DNA in Motor Neuron Disease Completed NCT00362362
13 Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS) Completed NCT00677768
14 Physiologic Studies of Spasticity Completed NCT00014976
15 Phenotype, Genotype & Biomarkers in ALS and Related Disorders Recruiting NCT02327845
16 Acoustic and Perceptual Markers of Dysarthria in Amyotrophic Lateral Sclerosis (ALS) Recruiting NCT03560661
17 Clinical Procedures to Support Research Recruiting NCT03489278
18 Genetics of Familial and Sporadic ALS Recruiting NCT00821132
19 TRIAL READY (Clinical Trial Readiness) Recruiting NCT03912987
20 Genomic Translation for Amyotrophic Lateral Sclerosis Care Recruiting NCT02795897
21 Imaging Biomarkers in ALS Active, not recruiting NCT02567136
22 Answer ALS: Individualized Initiative for ALS Discovery Active, not recruiting NCT02574390
23 A Patient Centric Motor Neuron Disease Activities of Daily Living Scale Enrolling by invitation NCT02852278

Search NIH Clinical Center for Primary Lateral Sclerosis, Adult, 1

Genetic Tests for Primary Lateral Sclerosis, Adult, 1

Anatomical Context for Primary Lateral Sclerosis, Adult, 1

MalaCards organs/tissues related to Primary Lateral Sclerosis, Adult, 1:

42
Brain, Testes, Cortex, Spinal Cord, Prostate, Bone, Monocytes

Publications for Primary Lateral Sclerosis, Adult, 1

Articles related to Primary Lateral Sclerosis, Adult, 1:

# Title Authors Year
1
Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis. ( 27123479 )
2016
2
Adult-onset primary lateral sclerosis is not associated with mutations in the ALS2 gene. ( 17698795 )
2007

Variations for Primary Lateral Sclerosis, Adult, 1

Expression for Primary Lateral Sclerosis, Adult, 1

Search GEO for disease gene expression data for Primary Lateral Sclerosis, Adult, 1.

Pathways for Primary Lateral Sclerosis, Adult, 1

Pathways related to Primary Lateral Sclerosis, Adult, 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.87 MAPT SNCA SOD1
2 10.69 MAPT SOD1
3 10.09 ARHGEF2 MAPT

GO Terms for Primary Lateral Sclerosis, Adult, 1

Cellular components related to Primary Lateral Sclerosis, Adult, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuron projection GO:0043005 9.54 ALS2 MAPT SOD1
2 axon GO:0030424 9.5 ALS2 MAPT SNCA
3 microtubule GO:0005874 9.43 ARHGEF2 MAPT SPAST
4 mitochondrial intermembrane space GO:0005758 9.4 SNCA SOD1
5 neuronal cell body GO:0043025 9.35 ALS2 ARHGEF2 MAPT SNCA SOD1
6 growth cone GO:0030426 9.33 ALS2 MAPT SNCA
7 axon cytoplasm GO:1904115 8.92 MAPT SOD1 SPAST SPG7

Biological processes related to Primary Lateral Sclerosis, Adult, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.65 ARHGEF2 SNCA SOD1
2 positive regulation of protein serine/threonine kinase activity GO:0071902 9.46 ALS2 SNCA
3 synapse organization GO:0050808 9.43 MAPT SNCA
4 cytoplasmic microtubule organization GO:0031122 9.4 MAPT SPAST
5 positive regulation of neuron death GO:1901216 9.37 MAPT SNCA
6 microglial cell activation GO:0001774 9.32 MAPT SNCA
7 positive regulation of superoxide anion generation GO:0032930 9.26 MAPT SOD1
8 supramolecular fiber organization GO:0097435 9.16 MAPT SNCA
9 axonal transport of mitochondrion GO:0019896 8.96 MAPT SPAST
10 anterograde axonal transport GO:0008089 8.8 SOD1 SPAST SPG7

Molecular functions related to Primary Lateral Sclerosis, Adult, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 zinc ion binding GO:0008270 9.62 ARHGEF2 SNCA SOD1 SPG7
2 enzyme binding GO:0019899 9.61 MAPT SNCA SOD1
3 Rho guanyl-nucleotide exchange factor activity GO:0005089 9.46 ALS2 ARHGEF2
4 copper ion binding GO:0005507 9.4 SNCA SOD1
5 Rac GTPase binding GO:0048365 9.37 ARHGEF2 SOD1
6 beta-tubulin binding GO:0048487 9.26 SNCA SPAST
7 alpha-tubulin binding GO:0043014 9.16 SNCA SPAST
8 Rac guanyl-nucleotide exchange factor activity GO:0030676 8.96 ALS2 ARHGEF2
9 microtubule binding GO:0008017 8.92 ARHGEF2 MAPT SNCA SPAST

Sources for Primary Lateral Sclerosis, Adult, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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