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Juvenile amyotrophic lateral sclerosis(JALS)

MedGen UID:
923704
•Concept ID:
C3468114
•
Disease or Syndrome
Synonym: JALS
SNOMED CT: Juvenile amyotrophic lateral sclerosis (718555006); JALS - juvenile amyotrophic lateral sclerosis (718555006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related genes: SPG11, ALS2, SIGMAR1
 
Monarch Initiative: MONDO:0017593
Orphanet: ORPHA300605

Definition

A very rare severe motor neuron disease with manifestation of progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age. The disease is usually slowly progressive and some patients have been reported to become bedridden by 12 to 50 years of age. Mutations in the following genes have been found in patients ALS2 (2q33-q35), and rarely SIGMAR1 (9p13.3), SPG11 (15q13-q15) and FUS (16p11.2). [from SNOMEDCT_US]

Professional guidelines

PubMed

Genotype-phenotype correlation in seven motor neuron disease families with novel ALS2 mutations.
Sprute R, Jergas H, Ölmez A, Alawbathani S, Karasoy H, Dafsari HS, Becker K, Daimagüler HS, Nürnberg P, Muntoni F, Topaloglu H, Uyanik G, Cirak S
Am J Med Genet A 2021 Feb;185(2):344-354. Epub 2020 Nov 5 doi: 10.1002/ajmg.a.61951. PMID: 33155358

Recent clinical studies

Etiology

Serine Palmitoyltransferase (SPT)-related Neurodegenerative and Neurodevelopmental Disorders.
Mohassel P, Abdullah M, Eichler FS, Dunn TM
J Neuromuscul Dis 2024;11(4):735-747. doi: 10.3233/JND-240014. PMID: 38788085Free PMC Article
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
Proximity-based labeling reveals DNA damage-induced phosphorylation of fused in sarcoma (FUS) causes distinct changes in the FUS protein interactome.
Johnson MA, Nuckols TA, Merino P, Bagchi P, Nandy S, Root J, Taylor G, Seyfried NT, Kukar T
J Biol Chem 2022 Aug;298(8):102135. Epub 2022 Jun 14 doi: 10.1016/j.jbc.2022.102135. PMID: 35709984Free PMC Article
Juvenile Amyotrophic Lateral Sclerosis: A Review.
Lehky T, Grunseich C
Genes (Basel) 2021 Nov 30;12(12) doi: 10.3390/genes12121935. PMID: 34946884Free PMC Article
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Montecchiani C, Pedace L, Lo Giudice T, Casella A, Mearini M, Gaudiello F, Pedroso JL, Terracciano C, Caltagirone C, Massa R, St George-Hyslop PH, Barsottini OG, Kawarai T, Orlacchio A
Brain 2016 Jan;139(Pt 1):73-85. Epub 2015 Nov 10 doi: 10.1093/brain/awv320. PMID: 26556829Free PMC Article

Diagnosis

Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.
Souza PVS, Serrano PL, Farias IB, Machado RIL, Badia BML, Oliveira HB, Barbosa AS, Pereira CA, Moreira VF, Chieia MAT, Barbosa AR, Braga VL, Pinto WBVR, Oliveira ASB
Genes (Basel) 2024 Feb 28;15(3) doi: 10.3390/genes15030311. PMID: 38540369Free PMC Article
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
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.
Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, Cookson MR, Sabir MS, Dalgard CL, Troakes C, Jones AR, Shatunov A, Iacoangeli A, Al Khleifat A, Ticozzi N, Silani V, Gellera C, Blair IP, Dobson-Stone C, Kwok JB, Bonkowski ES, Palvadeau R, Tienari PJ, Morrison KE, Shaw PJ, Al-Chalabi A, Brown RH Jr, Calvo A, Mora G, Al-Saif H, Gotkine M, Leigh F, Chang IJ, Perlman SJ, Glass I, Scott AI, Shaw CE, Basak AN, Landers JE, Chiò A, Crawford TO, Smith BN, Traynor BJ; FALS Sequencing Consortium; American Genome Center; International ALS Genomics Consortium; and ITALSGEN Consortium, Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp SD, Scotter EL, Kenna KP, Keagle P, Tiloca C, Vance C, Troakes C, Colombrita C, King A, Pensato V, Castellotti B, Baas F, Ten Asbroek ALMA, McKenna-Yasek D, McLaughlin RL, Polak M, Asress S, Esteban-Pérez J, Stevic Z, D'Alfonso S, Mazzini L, Comi GP, Del Bo R, Ceroni M, Gagliardi S, Querin G, Bertolin C, van Rheenen W, Rademakers R, van Blitterswijk M, Lauria G, Duga S, Corti S, Cereda C, Corrado L, Sorarù G, Williams KL, Nicholson GA, Blair IP, Leblond-Manry C, Rouleau GA, Hardiman O, Morrison KE, Veldink JH, van den Berg LH, Al-Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García-Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH Jr, Silani V, Shaw CE, Landers JE, Dalgard CL, Adeleye A, Soltis AR, Alba C, Viollet C, Bacikova D, Hupalo DN, Sukumar G, Pollard HB, Wilkerson MD, Martinez EM, Abramzon Y, Ahmed S, Arepalli S, Baloh RH, Bowser R, Brady CB, Brice A, Broach J, Campbell RH, Camu W, Chia R, Cooper-Knock J, Ding J, Drepper C, Drory VE, Dunckley TL, Eicher JD, England BK, Faghri F, Feldman E, Floeter MK, Fratta P, Geiger JT, Gerhard G, Gibbs JR, Gibson SB, Glass JD, Hardy J, Harms MB, Heiman-Patterson TD, Hernandez DG, Jansson L, Kirby J, Kowall NW, Laaksovirta H, Landeck N, Landi F, Le Ber I, Lumbroso S, MacGowan DJL, Maragakis NJ, Mora G, Mouzat K, Murphy NA, Myllykangas L, Nalls MA, Orrell RW, Ostrow LW, Pamphlett R, Pickering-Brown S, Pioro EP, Pletnikova O, Pliner HA, Pulst SM, Ravits JM, Renton AE, Rivera A, Robberecht W, Rogaeva E, Rollinson S, Rothstein JD, Scholz SW, Sendtner M, Shaw PJ, Sidle KC, Simmons Z, Singleton AB, Smith N, Stone DJ, Tienari PJ, Troncoso JC, Valori M, Van Damme P, Van Deerlin VM, Van Den Bosch L, Zinman L, Landers JE, Chiò A, Traynor BJ, Angelocola SM, Ausiello FP, Barberis M, Bartolomei I, Battistini S, Bersano E, Bisogni G, Borghero G, Brunetti M, Cabona C, Calvo A, Canale F, Canosa A, Cantisani TA, Capasso M, Caponnetto C, Cardinali P, Carrera P, Casale F, Chiò A, Colletti T, Conforti FL, Conte A, Conti E, Corbo M, Cuccu S, Dalla Bella E, D'Errico E, DeMarco G, Dubbioso R, Ferrarese C, Ferraro PM, Filippi M, Fini N, Floris G, Fuda G, Gallone S, Gianferrari G, Giannini F, Grassano M, Greco L, Iazzolino B, Introna A, La Bella V, Lattante S, Lauria G, Liguori R, Logroscino G, Logullo FO, Lunetta C, Mandich P, Mandrioli J, Manera U, Manganelli F, Marangi G, Marinou K, Marrosu MG, Martinelli I, Messina S, Moglia C, Mora G, Mosca L, Murru MR, Origone P, Passaniti C, Petrelli C, Petrucci A, Pozzi S, Pugliatti M, Quattrini A, Ricci C, Riolo G, Riva N, Russo M, Sabatelli M, Salamone P, Salivetto M, Salvi F, Santarelli M, Sbaiz L, Sideri R, Simone I, Simonini C, Spataro R, Tanel R, Tedeschi G, Ticca A, Torriello A, Tranquilli S, Tremolizzo L, Trojsi F, Vasta R, Vacchiano V, Vita G, Volanti P, Zollino M, Zucchi E
JAMA Neurol 2021 Oct 1;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874Free PMC Article
Juvenile amyotrophic lateral sclerosis with complex phenotypes associated with novel SYNE1 mutations.
Naruse H, Ishiura H, Mitsui J, Takahashi Y, Matsukawa T, Toda T, Tsuji S
Amyotroph Lateral Scler Frontotemporal Degener 2021 Nov;22(7-8):576-578. Epub 2020 Sep 1 doi: 10.1080/21678421.2020.1813312. PMID: 32870032
A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
Siddiqi S, Foo JN, Vu A, Azim S, Silver DL, Mansoor A, Tay SK, Abbasi S, Hashmi AH, Janjua J, Khalid S, Tai ES, Yeo GW, Khor CC
PLoS One 2014;9(12):e113258. Epub 2014 Dec 4 doi: 10.1371/journal.pone.0113258. PMID: 25474699Free PMC Article

Therapy

A juvenile ALS-like phenotype dramatically improved after high-dose riboflavin treatment.
Carreau C, Lenglet T, Mosnier I, Lahlou G, Fargeot G, Weiss N, Demeret S, Salachas F, Veauville-Merllié A, Acquaviva C, Nadjar Y
Ann Clin Transl Neurol 2020 Feb;7(2):250-253. Epub 2020 Feb 5 doi: 10.1002/acn3.50977. PMID: 32022482Free PMC Article
Adult-onset motor neuron disease with basophilic intraneuronal inclusion bodies.
Kusaka H, Matsumoto S, Imai T
Clin Neuropathol 1993 Jul-Aug;12(4):215-8. PMID: 8403632

Prognosis

Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges.
Souza PVS, Serrano PL, Farias IB, Machado RIL, Badia BML, Oliveira HB, Barbosa AS, Pereira CA, Moreira VF, Chieia MAT, Barbosa AR, Braga VL, Pinto WBVR, Oliveira ASB
Genes (Basel) 2024 Feb 28;15(3) doi: 10.3390/genes15030311. PMID: 38540369Free PMC Article
Juvenile Amyotrophic Lateral Sclerosis: A Review.
Lehky T, Grunseich C
Genes (Basel) 2021 Nov 30;12(12) doi: 10.3390/genes12121935. PMID: 34946884Free PMC Article
A rare case of juvenile amyotrophic lateral sclerosis.
Bodur M, Toker RT, Başak AN, Okan MS
Turk J Pediatr 2021;63(3):495-499. doi: 10.24953/turkjped.2021.03.017. PMID: 34254495
Juvenile amyotrophic lateral sclerosis with complex phenotypes associated with novel SYNE1 mutations.
Naruse H, Ishiura H, Mitsui J, Takahashi Y, Matsukawa T, Toda T, Tsuji S
Amyotroph Lateral Scler Frontotemporal Degener 2021 Nov;22(7-8):576-578. Epub 2020 Sep 1 doi: 10.1080/21678421.2020.1813312. PMID: 32870032
A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
Siddiqi S, Foo JN, Vu A, Azim S, Silver DL, Mansoor A, Tay SK, Abbasi S, Hashmi AH, Janjua J, Khalid S, Tai ES, Yeo GW, Khor CC
PLoS One 2014;9(12):e113258. Epub 2014 Dec 4 doi: 10.1371/journal.pone.0113258. PMID: 25474699Free PMC Article

Clinical prediction guides

Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.
Liu Y, He X, Yuan Y, Li B, Liu Z, Li W, Li K, Tan S, Zhu Q, Tang Z, Han F, Wu Z, Shen L, Jiang H, Tang B, Qiu J, Hu Z, Wang J
Front Med 2024 Feb;18(1):68-80. Epub 2023 Oct 24 doi: 10.1007/s11684-023-1005-y. PMID: 37874476
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis.
Johnson JO, Chia R, Miller DE, Li R, Kumaran R, Abramzon Y, Alahmady N, Renton AE, Topp SD, Gibbs JR, Cookson MR, Sabir MS, Dalgard CL, Troakes C, Jones AR, Shatunov A, Iacoangeli A, Al Khleifat A, Ticozzi N, Silani V, Gellera C, Blair IP, Dobson-Stone C, Kwok JB, Bonkowski ES, Palvadeau R, Tienari PJ, Morrison KE, Shaw PJ, Al-Chalabi A, Brown RH Jr, Calvo A, Mora G, Al-Saif H, Gotkine M, Leigh F, Chang IJ, Perlman SJ, Glass I, Scott AI, Shaw CE, Basak AN, Landers JE, Chiò A, Crawford TO, Smith BN, Traynor BJ; FALS Sequencing Consortium; American Genome Center; International ALS Genomics Consortium; and ITALSGEN Consortium, Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp SD, Scotter EL, Kenna KP, Keagle P, Tiloca C, Vance C, Troakes C, Colombrita C, King A, Pensato V, Castellotti B, Baas F, Ten Asbroek ALMA, McKenna-Yasek D, McLaughlin RL, Polak M, Asress S, Esteban-Pérez J, Stevic Z, D'Alfonso S, Mazzini L, Comi GP, Del Bo R, Ceroni M, Gagliardi S, Querin G, Bertolin C, van Rheenen W, Rademakers R, van Blitterswijk M, Lauria G, Duga S, Corti S, Cereda C, Corrado L, Sorarù G, Williams KL, Nicholson GA, Blair IP, Leblond-Manry C, Rouleau GA, Hardiman O, Morrison KE, Veldink JH, van den Berg LH, Al-Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García-Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH Jr, Silani V, Shaw CE, Landers JE, Dalgard CL, Adeleye A, Soltis AR, Alba C, Viollet C, Bacikova D, Hupalo DN, Sukumar G, Pollard HB, Wilkerson MD, Martinez EM, Abramzon Y, Ahmed S, Arepalli S, Baloh RH, Bowser R, Brady CB, Brice A, Broach J, Campbell RH, Camu W, Chia R, Cooper-Knock J, Ding J, Drepper C, Drory VE, Dunckley TL, Eicher JD, England BK, Faghri F, Feldman E, Floeter MK, Fratta P, Geiger JT, Gerhard G, Gibbs JR, Gibson SB, Glass JD, Hardy J, Harms MB, Heiman-Patterson TD, Hernandez DG, Jansson L, Kirby J, Kowall NW, Laaksovirta H, Landeck N, Landi F, Le Ber I, Lumbroso S, MacGowan DJL, Maragakis NJ, Mora G, Mouzat K, Murphy NA, Myllykangas L, Nalls MA, Orrell RW, Ostrow LW, Pamphlett R, Pickering-Brown S, Pioro EP, Pletnikova O, Pliner HA, Pulst SM, Ravits JM, Renton AE, Rivera A, Robberecht W, Rogaeva E, Rollinson S, Rothstein JD, Scholz SW, Sendtner M, Shaw PJ, Sidle KC, Simmons Z, Singleton AB, Smith N, Stone DJ, Tienari PJ, Troncoso JC, Valori M, Van Damme P, Van Deerlin VM, Van Den Bosch L, Zinman L, Landers JE, Chiò A, Traynor BJ, Angelocola SM, Ausiello FP, Barberis M, Bartolomei I, Battistini S, Bersano E, Bisogni G, Borghero G, Brunetti M, Cabona C, Calvo A, Canale F, Canosa A, Cantisani TA, Capasso M, Caponnetto C, Cardinali P, Carrera P, Casale F, Chiò A, Colletti T, Conforti FL, Conte A, Conti E, Corbo M, Cuccu S, Dalla Bella E, D'Errico E, DeMarco G, Dubbioso R, Ferrarese C, Ferraro PM, Filippi M, Fini N, Floris G, Fuda G, Gallone S, Gianferrari G, Giannini F, Grassano M, Greco L, Iazzolino B, Introna A, La Bella V, Lattante S, Lauria G, Liguori R, Logroscino G, Logullo FO, Lunetta C, Mandich P, Mandrioli J, Manera U, Manganelli F, Marangi G, Marinou K, Marrosu MG, Martinelli I, Messina S, Moglia C, Mora G, Mosca L, Murru MR, Origone P, Passaniti C, Petrelli C, Petrucci A, Pozzi S, Pugliatti M, Quattrini A, Ricci C, Riolo G, Riva N, Russo M, Sabatelli M, Salamone P, Salivetto M, Salvi F, Santarelli M, Sbaiz L, Sideri R, Simone I, Simonini C, Spataro R, Tanel R, Tedeschi G, Ticca A, Torriello A, Tranquilli S, Tremolizzo L, Trojsi F, Vasta R, Vacchiano V, Vita G, Volanti P, Zollino M, Zucchi E
JAMA Neurol 2021 Oct 1;78(10):1236-1248. doi: 10.1001/jamaneurol.2021.2598. PMID: 34459874Free PMC Article
Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations.
Khani M, Shamshiri H, Fatehi F, Rohani M, Haghi Ashtiani B, Akhoundi FH, Alavi A, Moazzeni H, Taheri H, Ghani MT, Javanparast L, Hashemi SS, Haji-Seyed-Javadi R, Heidari M, Nafissi S, Elahi E
Mol Genet Genomic Med 2020 Jul;8(7):e1240. Epub 2020 May 8 doi: 10.1002/mgg3.1240. PMID: 32383541Free PMC Article
Interaction of amyotrophic lateral sclerosis/frontotemporal lobar degeneration-associated fused-in-sarcoma with proteins involved in metabolic and protein degradation pathways.
Wang T, Jiang X, Chen G, Xu J
Neurobiol Aging 2015 Jan;36(1):527-35. Epub 2014 Aug 4 doi: 10.1016/j.neurobiolaging.2014.07.044. PMID: 25192599
A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
Siddiqi S, Foo JN, Vu A, Azim S, Silver DL, Mansoor A, Tay SK, Abbasi S, Hashmi AH, Janjua J, Khalid S, Tai ES, Yeo GW, Khor CC
PLoS One 2014;9(12):e113258. Epub 2014 Dec 4 doi: 10.1371/journal.pone.0113258. PMID: 25474699Free PMC Article

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