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Amyotrophic lateral sclerosis type 16(ALS16)

MedGen UID:
482217
Concept ID:
C3280587
Disease or Syndrome
Synonym: Amyotrophic lateral sclerosis 16, juvenile
 
Gene (location): SIGMAR1 (9p13.3)
 
Monarch Initiative: MONDO:0013715
OMIM®: 614373

Definition

Any amyotrophic lateral sclerosis in which the cause of the disease is a mutation in the SIGMAR1 gene. [from MONDO]

Clinical features

From HPO
Weakness of the intrinsic hand muscles
MedGen UID:
322432
Concept ID:
C1834536
Finding
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Amyotrophic lateral sclerosis
MedGen UID:
274
Concept ID:
C0002736
Disease or Syndrome
Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor neurons, which are specialized nerve cells that control muscle movement. These nerve cells are found in the spinal cord and the brain. In ALS, motor neurons die (atrophy) over time, leading to muscle weakness, a loss of muscle mass, and an inability to control movement.\n\nThere are many different types of ALS; these types are distinguished by their signs and symptoms and their genetic cause or lack of clear genetic association. Most people with ALS have a form of the condition that is described as sporadic, which means it occurs in people with no apparent history of the disorder in their family. People with sporadic ALS usually first develop features of the condition in their late fifties or early sixties. A small proportion of people with ALS, estimated at 5 to 10 percent, have a family history of ALS or a related condition called frontotemporal dementia (FTD), which is a progressive brain disorder that affects personality, behavior, and language. The signs and symptoms of familial ALS typically first appear in one's late forties or early fifties. Rarely, people with familial ALS develop symptoms in childhood or their teenage years. These individuals have a rare form of the disorder known as juvenile ALS.\n\nThe first signs and symptoms of ALS may be so subtle that they are overlooked. The earliest symptoms include muscle twitching, cramping, stiffness, or weakness. Affected individuals may develop slurred speech (dysarthria) and, later, difficulty chewing or swallowing (dysphagia). Many people with ALS experience malnutrition because of reduced food intake due to dysphagia and an increase in their body's energy demands (metabolism) due to prolonged illness. Muscles become weaker as the disease progresses, and arms and legs begin to look thinner as muscle tissue atrophies. Individuals with ALS eventually lose muscle strength and the ability to walk. Affected individuals eventually become wheelchair-dependent and increasingly require help with personal care and other activities of daily living. Over time, muscle weakness causes affected individuals to lose the use of their hands and arms. Breathing becomes difficult because the muscles of the respiratory system weaken. Most people with ALS die from respiratory failure within 2 to 10 years after the signs and symptoms of ALS first appear; however, disease progression varies widely among affected individuals.\n\nApproximately 20 percent of individuals with ALS also develop FTD. Changes in personality and behavior may make it difficult for affected individuals to interact with others in a socially appropriate manner. Communication skills worsen as the disease progresses. It is unclear how the development of ALS and FTD are related. Individuals who develop both conditions are diagnosed as having ALS-FTD.\n\nA rare form of ALS that often runs in families is known as ALS-parkinsonism-dementia complex (ALS-PDC). This disorder is characterized by the signs and symptoms of ALS, in addition to a pattern of movement abnormalities known as parkinsonism, and a progressive loss of intellectual function (dementia). Signs of parkinsonism include unusually slow movements (bradykinesia), stiffness, and tremors. Affected members of the same family can have different combinations of signs and symptoms.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.

Professional guidelines

PubMed

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
Wadman RI, van der Pol WL, Bosboom WM, Asselman FL, van den Berg LH, Iannaccone ST, Vrancken AF
Cochrane Database Syst Rev 2019 Dec 11;12(12):CD006281. doi: 10.1002/14651858.CD006281.pub5. PMID: 31825542Free PMC Article
Goldman JS, Van Deerlin VM
Mol Diagn Ther 2018 Oct;22(5):505-513. doi: 10.1007/s40291-018-0347-7. PMID: 29971646Free PMC Article

Curated

Orphanet, Amyotrophic lateral sclerosis, 2007

Recent clinical studies

Etiology

Soto-Lara M, Silva-Loredo M, Monroy-Córdoba JR, Flores-Ordoñez P, Cervera-Delgadillo NG, Carrillo-Mora P
Complement Ther Med 2023 May;73:102932. Epub 2023 Feb 15 doi: 10.1016/j.ctim.2023.102932. PMID: 36805318
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Heidari ME, Nadali J, Parouhan A, Azarafraz M, Tabatabai SM, Irvani SSN, Eskandari F, Gharebaghi A
J Affect Disord 2021 May 15;287:182-190. Epub 2021 Mar 12 doi: 10.1016/j.jad.2021.03.015. PMID: 33799036
Mariosa D, Kamel F, Bellocco R, Ye W, Fang F
Eur J Neurol 2015 Nov;22(11):1436-42. Epub 2015 Jan 19 doi: 10.1111/ene.12632. PMID: 25600257Free PMC Article

Diagnosis

Scekic-Zahirovic J, Benetton C, Brunet A, Ye X, Logunov E, Douchamps V, Megat S, Andry V, Kan VWY, Stuart-Lopez G, Gilet J, Guillot SJ, Dirrig-Grosch S, Gorin C, Trombini M, Dieterle S, Sinniger J, Fischer M, René F, Gunes Z, Kessler P, Dupuis L, Pradat PF, Goumon Y, Goutagny R, Marchand-Pauvert V, Liebscher S, Rouaux C
Sci Transl Med 2024 Mar 13;16(738):eadg3665. doi: 10.1126/scitranslmed.adg3665. PMID: 38478631
de Alcântara C, Cruzeiro MM, França MC Jr, Alencar MA, Jaeger A, de Araújo CM, da Gama NAS, Camargos ST, de Souza LC
Muscle Nerve 2023 Sep;68(3):316-322. Epub 2023 Jul 10 doi: 10.1002/mus.27927. PMID: 37424512
Rutkove SB, Le M, Ruehr SA, Nagy JA, Semple C, Sanchez B
Muscle Nerve 2022 Jun;65(6):702-708. Epub 2022 Apr 14 doi: 10.1002/mus.27551. PMID: 35383969
Pasetto L, Callegaro S, Corbelli A, Fiordaliso F, Ferrara D, Brunelli L, Sestito G, Pastorelli R, Bianchi E, Cretich M, Chiari M, Potrich C, Moglia C, Corbo M, Sorarù G, Lunetta C, Calvo A, Chiò A, Mora G, Pennuto M, Quattrone A, Rinaldi F, D'Agostino VG, Basso M, Bonetto V
Mol Neurodegener 2021 Aug 10;16(1):52. doi: 10.1186/s13024-021-00470-3. PMID: 34376243Free PMC Article
Kioumourtzoglou MA, Rotem RS, Seals RM, Gredal O, Hansen J, Weisskopf MG
JAMA Neurol 2015 Aug;72(8):905-11. doi: 10.1001/jamaneurol.2015.0910. PMID: 26030836Free PMC Article

Therapy

Ly CV, Ireland MD, Self WK, Bollinger J, Jockel-Balsarotti J, Herzog H, Allred P, Miller L, Doyle M, Anez-Bruzual I, Trikamji B, Hyman T, Kung T, Nicholson K, Bucelli RC, Patterson BW, Bateman RJ, Miller TM
Ann Clin Transl Neurol 2023 Jun;10(6):1012-1024. Epub 2023 Apr 29 doi: 10.1002/acn3.51784. PMID: 37119480Free PMC Article
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF
Lancet Neurol 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7. PMID: 36804094
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Heidari ME, Nadali J, Parouhan A, Azarafraz M, Tabatabai SM, Irvani SSN, Eskandari F, Gharebaghi A
J Affect Disord 2021 May 15;287:182-190. Epub 2021 Mar 12 doi: 10.1016/j.jad.2021.03.015. PMID: 33799036

Prognosis

Chiò A, Moglia C, Canosa A, Manera U, Grassano M, Vasta R, Palumbo F, Gallone S, Brunetti M, Barberis M, De Marchi F, Dalgard C, Chia R, Mora G, Iazzolino B, Peotta L, Traynor BJ, Corrado L, D'Alfonso S, Mazzini L, Calvo A
Neurology 2023 Jul 4;101(1):e83-e93. Epub 2023 May 18 doi: 10.1212/WNL.0000000000207367. PMID: 37202167Free PMC Article
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF
Lancet Neurol 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7. PMID: 36804094
Tavazzi E, Gatta R, Vallati M, Cotti Piccinelli S, Filosto M, Padovani A, Castellano M, Di Camillo B
BMC Med Inform Decis Mak 2023 Feb 2;22(Suppl 6):346. doi: 10.1186/s12911-023-02113-7. PMID: 36732801Free PMC Article
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Chiò A, Mora G, Lauria G
Lancet Neurol 2017 Feb;16(2):144-157. Epub 2016 Dec 8 doi: 10.1016/S1474-4422(16)30358-1. PMID: 27964824

Clinical prediction guides

Ly CV, Ireland MD, Self WK, Bollinger J, Jockel-Balsarotti J, Herzog H, Allred P, Miller L, Doyle M, Anez-Bruzual I, Trikamji B, Hyman T, Kung T, Nicholson K, Bucelli RC, Patterson BW, Bateman RJ, Miller TM
Ann Clin Transl Neurol 2023 Jun;10(6):1012-1024. Epub 2023 Apr 29 doi: 10.1002/acn3.51784. PMID: 37119480Free PMC Article
Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF
Lancet Neurol 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7. PMID: 36804094
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Chiò A, Mora G, Lauria G
Lancet Neurol 2017 Feb;16(2):144-157. Epub 2016 Dec 8 doi: 10.1016/S1474-4422(16)30358-1. PMID: 27964824

Recent systematic reviews

Soto-Lara M, Silva-Loredo M, Monroy-Córdoba JR, Flores-Ordoñez P, Cervera-Delgadillo NG, Carrillo-Mora P
Complement Ther Med 2023 May;73:102932. Epub 2023 Feb 15 doi: 10.1016/j.ctim.2023.102932. PMID: 36805318
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
Larsson SC, Burgess S
BMC Med 2021 Dec 15;19(1):320. doi: 10.1186/s12916-021-02188-x. PMID: 34906131Free PMC Article
Heidari ME, Nadali J, Parouhan A, Azarafraz M, Tabatabai SM, Irvani SSN, Eskandari F, Gharebaghi A
J Affect Disord 2021 May 15;287:182-190. Epub 2021 Mar 12 doi: 10.1016/j.jad.2021.03.015. PMID: 33799036
Hurwitz N, Radakovic R, Boyce E, Peryer G
Amyotroph Lateral Scler Frontotemporal Degener 2021 Nov;22(7-8):449-458. Epub 2021 Mar 4 doi: 10.1080/21678421.2021.1892765. PMID: 33661072

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