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Amyotrophic lateral sclerosis type 3(ALS3)

MedGen UID:
339829
•Concept ID:
C1847735
•
Disease or Syndrome
Synonym: ALS3
SNOMED CT: Amyotrophic lateral sclerosis type 3 (1201950008); ALS3 - amyotrophic lateral sclerosis type 3 (1201950008)
 
Monarch Initiative: MONDO:0011691
OMIM®: 606640

Definition

Amyotrophic lateral sclerosis-3 (ALS3) is a neurodegenerative disorder characterized by the death of motor neurons in the cortex, brainstem, and spinal cord, resulting in progressive muscle weakness and atrophy and death from respiratory failure, usually within 3 to 5 years of symptom onset (Brown, 1995). For a phenotypic description and a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400). [from OMIM]

Clinical features

From HPO
Lower limb muscle weakness
MedGen UID:
324478
•Concept ID:
C1836296
•
Finding
Weakness of the muscles of the legs.
See: Feature record | Search on this feature
Dementia
MedGen UID:
99229
•Concept ID:
C0497327
•
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
See: Feature record | Search on this feature
Cerebellar atrophy
MedGen UID:
196624
•Concept ID:
C0740279
•
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
See: Feature record | Search on this feature
Bulbar signs
MedGen UID:
347246
•Concept ID:
C1856507
•
Finding
See: Feature record | Search on this feature
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Professional guidelines

PubMed

ASOs are an effective treatment for disease-associated oligodendrocyte signatures in premanifest and symptomatic SCA3 mice.
Schuster KH, Zalon AJ, DiFranco DM, Putka AF, Stec NR, Jarrah SI, Naeem A, Haque Z, Zhang H, Guan Y, McLoughlin HS
Mol Ther 2024 May 1;32(5):1359-1372. Epub 2024 Feb 29 doi: 10.1016/j.ymthe.2024.02.033. PMID: 38429929Free PMC Article
Optimizing pharmacologic treatment for ALS to improve outcomes and quality of life.
Lynch K
Am J Manag Care 2023 Jun;29(7 Suppl):S112-S119. doi: 10.37765/ajmc.2023.89389. PMID: 37433092
Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article

Curated

Orphanet, Amyotrophic lateral sclerosis, 2007

Recent clinical studies

Etiology

Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity.
Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, Żekanowski C, Kuźma-Kozakiewicz M
Sci Rep 2022 Jan 7;12(1):103. doi: 10.1038/s41598-021-03891-8. PMID: 34996976Free PMC Article
A review of Mendelian randomization in amyotrophic lateral sclerosis.
Julian TH, Boddy S, Islam M, Kurz J, Whittaker KJ, Moll T, Harvey C, Zhang S, Snyder MP, McDermott C, Cooper-Knock J, Shaw PJ
Brain 2022 Apr 29;145(3):832-842. doi: 10.1093/brain/awab420. PMID: 34791088Free PMC Article
Altered perivascular fibroblast activity precedes ALS disease onset.
Månberg A, Skene N, Sanders F, Trusohamn M, Remnestål J, Szczepińska A, Aksoylu IS, Lönnerberg P, Ebarasi L, Wouters S, Lehmann M, Olofsson J, von Gohren Antequera I, Domaniku A, De Schaepdryver M, De Vocht J, Poesen K, Uhlén M, Anink J, Mijnsbergen C, Vergunst-Bosch H, Hübers A, Kläppe U, Rodriguez-Vieitez E, Gilthorpe JD, Hedlund E, Harris RA, Aronica E, Van Damme P, Ludolph A, Veldink J, Ingre C, Nilsson P, Lewandowski SA
Nat Med 2021 Apr;27(4):640-646. Epub 2021 Apr 15 doi: 10.1038/s41591-021-01295-9. PMID: 33859435Free PMC Article
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS.
Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, Balka KR, Calleja DJ, Moghaddas F, Ni E, McLean CA, Samson AL, Tyebji S, Tonkin CJ, Bye CR, Turner BJ, Pepin G, Gantier MP, Rogers KL, McArthur K, Crouch PJ, Masters SL
Cell 2020 Oct 29;183(3):636-649.e18. Epub 2020 Oct 7 doi: 10.1016/j.cell.2020.09.020. PMID: 33031745Free PMC Article

Diagnosis

Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
ISG15 and ISGylation in Human Diseases.
Mirzalieva O, Juncker M, Schwartzenburg J, Desai S
Cells 2022 Feb 4;11(3) doi: 10.3390/cells11030538. PMID: 35159348Free PMC Article
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity.
Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, Żekanowski C, Kuźma-Kozakiewicz M
Sci Rep 2022 Jan 7;12(1):103. doi: 10.1038/s41598-021-03891-8. PMID: 34996976Free PMC Article
Altered perivascular fibroblast activity precedes ALS disease onset.
Månberg A, Skene N, Sanders F, Trusohamn M, Remnestål J, Szczepińska A, Aksoylu IS, Lönnerberg P, Ebarasi L, Wouters S, Lehmann M, Olofsson J, von Gohren Antequera I, Domaniku A, De Schaepdryver M, De Vocht J, Poesen K, Uhlén M, Anink J, Mijnsbergen C, Vergunst-Bosch H, Hübers A, Kläppe U, Rodriguez-Vieitez E, Gilthorpe JD, Hedlund E, Harris RA, Aronica E, Van Damme P, Ludolph A, Veldink J, Ingre C, Nilsson P, Lewandowski SA
Nat Med 2021 Apr;27(4):640-646. Epub 2021 Apr 15 doi: 10.1038/s41591-021-01295-9. PMID: 33859435Free PMC Article
Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.
Ng L, Khan F, Young CA, Galea M
Cochrane Database Syst Rev 2017 Jan 10;1(1):CD011776. doi: 10.1002/14651858.CD011776.pub2. PMID: 28072907Free PMC Article

Therapy

Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial.
Baudin E, Goichot B, Berruti A, Hadoux J, Moalla S, Laboureau S, Nölting S, de la Fouchardière C, Kienitz T, Deutschbein T, Zovato S, Amar L, Haissaguerre M, Timmers H, Niccoli P, Faggiano A, Angokai M, Lamartina L, Luca F, Cosentini D, Hahner S, Beuschlein F, Attard M, Texier M, Fassnacht M; ENDOCAN-COMETE; ENSAT Networks
Lancet 2024 Mar 16;403(10431):1061-1070. Epub 2024 Feb 22 doi: 10.1016/S0140-6736(23)02554-0. PMID: 38402886
Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study.
Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
A review of Mendelian randomization in amyotrophic lateral sclerosis.
Julian TH, Boddy S, Islam M, Kurz J, Whittaker KJ, Moll T, Harvey C, Zhang S, Snyder MP, McDermott C, Cooper-Knock J, Shaw PJ
Brain 2022 Apr 29;145(3):832-842. doi: 10.1093/brain/awab420. PMID: 34791088Free PMC Article
Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.
Ng L, Khan F, Young CA, Galea M
Cochrane Database Syst Rev 2017 Jan 10;1(1):CD011776. doi: 10.1002/14651858.CD011776.pub2. PMID: 28072907Free PMC Article

Prognosis

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study.
Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
ISG15 and ISGylation in Human Diseases.
Mirzalieva O, Juncker M, Schwartzenburg J, Desai S
Cells 2022 Feb 4;11(3) doi: 10.3390/cells11030538. PMID: 35159348Free PMC Article
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity.
Berdyński M, Miszta P, Safranow K, Andersen PM, Morita M, Filipek S, Żekanowski C, Kuźma-Kozakiewicz M
Sci Rep 2022 Jan 7;12(1):103. doi: 10.1038/s41598-021-03891-8. PMID: 34996976Free PMC Article
The spectrum of neurodevelopmental, neuromuscular and neurodegenerative disorders due to defective autophagy.
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Altered perivascular fibroblast activity precedes ALS disease onset.
Månberg A, Skene N, Sanders F, Trusohamn M, Remnestål J, Szczepińska A, Aksoylu IS, Lönnerberg P, Ebarasi L, Wouters S, Lehmann M, Olofsson J, von Gohren Antequera I, Domaniku A, De Schaepdryver M, De Vocht J, Poesen K, Uhlén M, Anink J, Mijnsbergen C, Vergunst-Bosch H, Hübers A, Kläppe U, Rodriguez-Vieitez E, Gilthorpe JD, Hedlund E, Harris RA, Aronica E, Van Damme P, Ludolph A, Veldink J, Ingre C, Nilsson P, Lewandowski SA
Nat Med 2021 Apr;27(4):640-646. Epub 2021 Apr 15 doi: 10.1038/s41591-021-01295-9. PMID: 33859435Free PMC Article

Clinical prediction guides

Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study.
Tang Y, Liu W, Kong W, Zhang S, Zhu T
Front Immunol 2023;14:1077088. Epub 2023 Feb 9 doi: 10.3389/fimmu.2023.1077088. PMID: 36845101Free PMC Article
Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Altered perivascular fibroblast activity precedes ALS disease onset.
Månberg A, Skene N, Sanders F, Trusohamn M, Remnestål J, Szczepińska A, Aksoylu IS, Lönnerberg P, Ebarasi L, Wouters S, Lehmann M, Olofsson J, von Gohren Antequera I, Domaniku A, De Schaepdryver M, De Vocht J, Poesen K, Uhlén M, Anink J, Mijnsbergen C, Vergunst-Bosch H, Hübers A, Kläppe U, Rodriguez-Vieitez E, Gilthorpe JD, Hedlund E, Harris RA, Aronica E, Van Damme P, Ludolph A, Veldink J, Ingre C, Nilsson P, Lewandowski SA
Nat Med 2021 Apr;27(4):640-646. Epub 2021 Apr 15 doi: 10.1038/s41591-021-01295-9. PMID: 33859435Free PMC Article
C9orf72 in myeloid cells suppresses STING-induced inflammation.
McCauley ME, O'Rourke JG, Yáñez A, Markman JL, Ho R, Wang X, Chen S, Lall D, Jin M, Muhammad AKMG, Bell S, Landeros J, Valencia V, Harms M, Arditi M, Jefferies C, Baloh RH
Nature 2020 Sep;585(7823):96-101. Epub 2020 Aug 19 doi: 10.1038/s41586-020-2625-x. PMID: 32814898Free PMC Article
Mitochondria-associated membranes in aging and senescence: structure, function, and dynamics.
Janikiewicz J, Szymański J, Malinska D, Patalas-Krawczyk P, Michalska B, Duszyński J, Giorgi C, Bonora M, Dobrzyn A, Wieckowski MR
Cell Death Dis 2018 Feb 28;9(3):332. doi: 10.1038/s41419-017-0105-5. PMID: 29491385Free PMC Article

Recent systematic reviews

Association between Galectin Levels and Neurodegenerative Diseases: Systematic Review and Meta-Analysis.
Ramos-Martínez E, Ramos-Martínez I, Sánchez-Betancourt I, Ramos-Martínez JC, Peña-Corona SI, Valencia J, Saucedo R, Almeida-Aguirre EKP, Cerbón M
Biomolecules 2022 Jul 31;12(8) doi: 10.3390/biom12081062. PMID: 36008956Free PMC Article
Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.
James E, Ellis C, Brassington R, Sathasivam S, Young CA
Cochrane Database Syst Rev 2022 May 20;5(5):CD006981. doi: 10.1002/14651858.CD006981.pub3. PMID: 35593746Free PMC Article
Burden of Neurological Disorders Across the US From 1990-2017: A Global Burden of Disease Study.
GBD 2017 US Neurological Disorders Collaborators, Feigin VL, Vos T, Alahdab F, Amit AML, Bärnighausen TW, Beghi E, Beheshti M, Chavan PP, Criqui MH, Desai R, Dhamminda Dharmaratne S, Dorsey ER, Wilder Eagan A, Elgendy IY, Filip I, Giampaoli S, Giussani G, Hafezi-Nejad N, Hole MK, Ikeda T, Owens Johnson C, Kalani R, Khatab K, Khubchandani J, Kim D, Koroshetz WJ, Krishnamoorthy V, Krishnamurthi RV, Liu X, Lo WD, Logroscino G, Mensah GA, Miller TR, Mohammed S, Mokdad AH, Moradi-Lakeh M, Morrison SD, Shivamurthy VKN, Naghavi M, Nichols E, Norrving B, Odell CM, Pupillo E, Radfar A, Roth GA, Shafieesabet A, Sheikh A, Sheikhbahaei S, Shin JI, Singh JA, Steiner TJ, Stovner LJ, Wallin MT, Weiss J, Wu C, Zunt JR, Adelson JD, Murray CJL
JAMA Neurol 2021 Feb 1;78(2):165-176. doi: 10.1001/jamaneurol.2020.4152. PMID: 33136137Free PMC Article
Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.
Ng L, Khan F, Young CA, Galea M
Cochrane Database Syst Rev 2017 Jan 10;1(1):CD011776. doi: 10.1002/14651858.CD011776.pub2. PMID: 28072907Free PMC Article
Rate of familial amyotrophic lateral sclerosis: a systematic review and meta-analysis.
Byrne S, Walsh C, Lynch C, Bede P, Elamin M, Kenna K, McLaughlin R, Hardiman O
J Neurol Neurosurg Psychiatry 2011 Jun;82(6):623-7. Epub 2010 Nov 3 doi: 10.1136/jnnp.2010.224501. PMID: 21047878

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