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Amyotrophic lateral sclerosis-parkinsonism-dementia complex

MedGen UID:
107775
Concept ID:
C0543859
Disease or Syndrome
Synonyms: Amyotrophic lateral sclerosis, Parkinsonism/Dementia complex of Guam; Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1; Guam disease
SNOMED CT: Amyotrophic lateral sclerosis, parkinsonism, dementia of Guam syndrome (838276009); Guam disease (838276009); Lytico Bodig disease (838276009); PDALS (parkinsonism, dementia, amyotrophic lateral sclerosis) complex (838276009); Amyotrophic lateral sclerosis, parkinsonism, dementia complex (838276009)
 
Gene (location): TRPM7 (15q21.2)
 
Monarch Initiative: MONDO:0007104
OMIM®: 105500
Orphanet: ORPHA90020

Definition

Amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam is a neurodegenerative disorder with unusually high incidence among the Chamorro people of Guam. Both ALS and parkinsonism-dementia are chronic, progressive, and uniformly fatal disorders in this population. Both diseases are known to occur in the same kindred, the same sibship, and even the same individual. See PARK7 (606324) for discussion of a similar phenotype caused by mutation in the DJ1 gene (602533). [from OMIM]

Clinical features

From HPO
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.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
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.
Paralysis
MedGen UID:
105510
Concept ID:
C0522224
Finding
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement.
Abnormal lower motor neuron morphology
MedGen UID:
356272
Concept ID:
C1865412
Finding
Any structural anomaly of the lower motor neuron.
Bulbar palsy
MedGen UID:
898626
Concept ID:
C4082299
Disease or Syndrome
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAmyotrophic lateral sclerosis-parkinsonism-dementia complex
Follow this link to review classifications for Amyotrophic lateral sclerosis-parkinsonism-dementia complex in Orphanet.

Professional guidelines

PubMed

Buée L, Pérez-Tur J, Leveugle B, Buée-Scherrer V, Mufson EJ, Loerzel AJ, Chartier-Harlin MC, Perl DP, Delacourte A, Hof PR
Acta Neuropathol 1996;91(3):247-53. doi: 10.1007/s004010050422. PMID: 8834536

Recent clinical studies

Etiology

Li M, Qiu J, Yan G, Zheng X, Li A
Sci Total Environ 2024 Apr 20;922:171255. Epub 2024 Feb 26 doi: 10.1016/j.scitotenv.2024.171255. PMID: 38417517
Cox PA, Kostrzewa RM, Guillemin GJ
Neurotox Res 2018 Jan;33(1):178-183. Epub 2017 May 24 doi: 10.1007/s12640-017-9753-6. PMID: 28540663
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Rivadeneyra-Domínguez E, Rodríguez-Landa JF
Neurologia 2014 Nov-Dec;29(9):517-22. Epub 2013 May 30 doi: 10.1016/j.nrl.2013.03.005. PMID: 23725821
Buée L, Pérez-Tur J, Leveugle B, Buée-Scherrer V, Mufson EJ, Loerzel AJ, Chartier-Harlin MC, Perl DP, Delacourte A, Hof PR
Acta Neuropathol 1996;91(3):247-53. doi: 10.1007/s004010050422. PMID: 8834536

Diagnosis

Kokubo Y, Morimoto S, Sasaki R, Hasegawa M, Ishiura H, Tsuji S, Yoshida M, Yamazoe N, Miyazaki M, Kuzuhara S
Neurol Sci 2022 Feb;43(2):1423-1425. Epub 2021 Nov 15 doi: 10.1007/s10072-021-05737-7. PMID: 34779964
Porojan C, Mitrovic SM, Yeo DC, Furey A
Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2016 Oct;33(10):1570-1586. Epub 2016 Sep 22 doi: 10.1080/19440049.2016.1217070. PMID: 27652898
Dombroski BA, Galasko DR, Mata IF, Zabetian CP, Craig UK, Garruto RM, Oyanagi K, Schellenberg GD
JAMA Neurol 2013 Jun;70(6):742-5. doi: 10.1001/jamaneurol.2013.1817. PMID: 23588498Free PMC Article
Tomiyama H, Kokubo Y, Sasaki R, Li Y, Imamichi Y, Funayama M, Mizuno Y, Hattori N, Kuzuhara S
Mov Disord 2008 Dec 15;23(16):2344-8. doi: 10.1002/mds.22262. PMID: 18759352
McGeer PL, Schwab C, McGeer EG, Haddock RL, Steele JC
Neurology 1997 Aug;49(2):400-9. doi: 10.1212/wnl.49.2.400. PMID: 9270568

Therapy

Gerić M, Gajski G, Domijan AM, Garaj-Vrhovac V, Filipič M, Žegura B
Chemosphere 2019 Jan;214:623-632. Epub 2018 Sep 27 doi: 10.1016/j.chemosphere.2018.09.155. PMID: 30290362
Rivadeneyra-Domínguez E, Rodríguez-Landa JF
Neurologia 2014 Nov-Dec;29(9):517-22. Epub 2013 May 30 doi: 10.1016/j.nrl.2013.03.005. PMID: 23725821
Tshala-Katumbay D, Mumba N, Okitundu L, Kazadi K, Banea M, Tylleskär T, Boivin M, Muyembe-Tamfum JJ
Neurology 2013 Mar 5;80(10):949-51. doi: 10.1212/WNL.0b013e3182840b81. PMID: 23460617Free PMC Article
Morimoto S, Kuzuhara S, Kokubo Y
Mov Disord 2009 Jan 15;24(1):123-6. doi: 10.1002/mds.22362. PMID: 18972548
Durlach J, Bac P, Durlach V, Durlach A, Bara M, Guiet-Bara A
Magnes Res 1997 Dec;10(4):339-53. PMID: 9513930

Prognosis

Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Tshala-Katumbay D, Mumba N, Okitundu L, Kazadi K, Banea M, Tylleskär T, Boivin M, Muyembe-Tamfum JJ
Neurology 2013 Mar 5;80(10):949-51. doi: 10.1212/WNL.0b013e3182840b81. PMID: 23460617Free PMC Article
Kuzuhara S, Kokubo Y
Mov Disord 2005 Aug;20 Suppl 12:S108-13. doi: 10.1002/mds.20548. PMID: 16092099
McGeer PL, Schwab C, McGeer EG, Haddock RL, Steele JC
Neurology 1997 Aug;49(2):400-9. doi: 10.1212/wnl.49.2.400. PMID: 9270568
Snow BJ, Peppard RF, Guttman M, Okada J, Martin WR, Steele J, Eisen A, Carr G, Schoenberg B, Calne D
Arch Neurol 1990 Aug;47(8):870-4. doi: 10.1001/archneur.1990.00530080052010. PMID: 2375693

Clinical prediction guides

Porojan C, Mitrovic SM, Yeo DC, Furey A
Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2016 Oct;33(10):1570-1586. Epub 2016 Sep 22 doi: 10.1080/19440049.2016.1217070. PMID: 27652898
Steele JC, Wresch R, Hanlon SD, Keystone J, Ben-Shlomo Y
Mov Disord 2015 Aug;30(9):1271-5. Epub 2015 Jul 7 doi: 10.1002/mds.26264. PMID: 26153661
Steele JC, Guella I, Szu-Tu C, Lin MK, Thompson C, Evans DM, Sherman HE, Vilariño-Güell C, Gwinn K, Morris H, Dickson DW, Farrer MJ
Ann Neurol 2015 Mar;77(3):458-68. Epub 2015 Feb 3 doi: 10.1002/ana.24346. PMID: 25558820
Buée L, Hof PR, Delacourte A
Ann N Y Acad Sci 1997 Sep 26;826:7-24. doi: 10.1111/j.1749-6632.1997.tb48457.x. PMID: 9329677
Buée-Scherrer V, Buée L, Hof PR, Leveugle B, Gilles C, Loerzel AJ, Perl DP, Delacourte A
Am J Pathol 1995 Apr;146(4):924-32. PMID: 7717459Free PMC Article

Recent systematic reviews

Lance E, Arnich N, Maignien T, Biré R
Toxins (Basel) 2018 Feb 14;10(2) doi: 10.3390/toxins10020083. PMID: 29443939Free PMC Article

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