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Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1(ALS-PDC)

MedGen UID:
107775
Concept ID:
C0543859
Disease or Syndrome
Synonyms: ALS-PDC; Amyotrophic lateral sclerosis, Parkinsonism/Dementia complex of Guam; Guam disease
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): TRPM7 (15q21.2)
OMIM®: 105500
Orphanet: ORPHA90020

Definition

Amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam is a neurodengenerative 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. [from OMIM]

Additional description

From GHR
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.There 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.The 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.Approximately 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.A 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.  https://ghr.nlm.nih.gov/condition/amyotrophic-lateral-sclerosis

Clinical features

Amyotrophic lateral sclerosis
MedGen UID:
274
Concept ID:
C0002736
Disease or Syndrome
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN). UMN signs include hyperreflexia, extensor plantar response, increased muscle tone, and weakness in a topographic representation. LMN signs include weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Initial presentation varies. Affected individuals typically present with either asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). Other findings may include muscle fasciculations, muscle cramps, and labile affect, but not necessarily mood. Regardless of initial symptoms, atrophy and weakness eventually affect other muscles. The mean age of onset is 56 years in individuals with no known family history and 46 years in individuals with more than one affected family member (familial ALS or FALS). Average disease duration is about three years, but it can vary significantly. Death usually results from compromise of the respiratory muscles.
Bulbar palsy
MedGen UID:
18290
Concept ID:
C0030442
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.
Parkinsonism
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting form 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
Dementia is the name for a group of symptoms caused by disorders that affect the brain. It is not a specific disease. People with dementia may not be able to think well enough to do normal activities, such as getting dressed or eating. They may lose their ability to solve problems or control their emotions. Their personalities may change. They may become agitated or see things that are not there. . Memory loss is a common symptom of dementia. However, memory loss by itself does not mean you have dementia. People with dementia have serious problems with two or more brain functions, such as memory and language. Although dementia is common in very elderly people, it is not part of normal aging. Many different diseases can cause dementia, including Alzheimer's disease and stroke. Drugs are available to treat some of these diseases. While these drugs cannot cure dementia or repair brain damage, they may improve symptoms or slow down the disease. NIH: National Institute of Neurological Disorders and Stroke.
Abnormal lower motor neuron morphology
MedGen UID:
356272
Concept ID:
C1865412
Finding
Any structural anomaly of the lower motor neuron.
Muscle cramps
MedGen UID:
7749
Concept ID:
C0026821
Sign or Symptom
Muscle cramps are sudden, involuntary contractions or spasms in one or more of your muscles. They often occur after exercise or at night, lasting a few seconds to several minutes. It is a very common muscle problem. . Muscle cramps can be caused by nerves that malfunction. Sometimes this malfunction is due to a health problem, such as a spinal cord injury or a pinched nerve in the neck or back. Other causes are. -Straining or overusing a muscle. -Dehydration. -A lack of minerals in your diet or the depletion of minerals in your body. -Not enough blood getting to your muscles. Cramps can be very painful. Stretching or gently massaging the muscle can relieve this pain. .
Bulbar palsy
MedGen UID:
18290
Concept ID:
C0030442
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.
Weakness
MedGen UID:
811372
Concept ID:
C3714552
Sign or Symptom
Reduced strength of muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAmyotrophic lateral sclerosis-parkinsonism/dementia complex 1
Follow this link to review classifications for Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 in Orphanet.

Recent clinical studies

Etiology

Canale A, Albera R, Lacilla M, Canosa A, Albera A, Sacco F, Chiò A, Calvo A
Eur Arch Otorhinolaryngol 2017 Feb;274(2):679-683. Epub 2016 Aug 30 doi: 10.1007/s00405-016-4284-y. PMID: 27577043
E M, Yu S, Dou J, Jin W, Cai X, Mao Y, Zhu D, Yang R
Neurol Sci 2016 Aug;37(8):1203-8. Epub 2016 Apr 21 doi: 10.1007/s10072-016-2575-0. PMID: 27103621
Vercruysse P, Sinniger J, El Oussini H, Scekic-Zahirovic J, Dieterlé S, Dengler R, Meyer T, Zierz S, Kassubek J, Fischer W, Dreyhaupt J, Grehl T, Hermann A, Grosskreutz J, Witting A, Van Den Bosch L, Spreux-Varoquaux O; GERP ALS Study Group., Ludolph AC, Dupuis L
Brain 2016 Apr;139(Pt 4):1106-22. Epub 2016 Mar 16 doi: 10.1093/brain/aww004. PMID: 26984187
Moura MC, Casulari LA, Carvalho Garbi Novaes MR
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):275-81. Epub 2016 Feb 5 doi: 10.3109/21678421.2016.1140210. PMID: 26850047
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

Diagnosis

Canale A, Albera R, Lacilla M, Canosa A, Albera A, Sacco F, Chiò A, Calvo A
Eur Arch Otorhinolaryngol 2017 Feb;274(2):679-683. Epub 2016 Aug 30 doi: 10.1007/s00405-016-4284-y. PMID: 27577043
E M, Yu S, Dou J, Jin W, Cai X, Mao Y, Zhu D, Yang R
Neurol Sci 2016 Aug;37(8):1203-8. Epub 2016 Apr 21 doi: 10.1007/s10072-016-2575-0. PMID: 27103621
Sako W, Abe T, Izumi Y, Harada M, Kaji R
J Clin Neurosci 2016 May;27:110-3. Epub 2016 Jan 4 doi: 10.1016/j.jocn.2015.08.044. PMID: 26765768
Cosottini M, Donatelli G, Costagli M, Caldarazzo Ienco E, Frosini D, Pesaresi I, Biagi L, Siciliano G, Tosetti M
AJNR Am J Neuroradiol 2016 Mar;37(3):455-61. Epub 2015 Dec 17 doi: 10.3174/ajnr.A4562. PMID: 26680464
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

Therapy

Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Shamshiri H, Fatehi F, Abolfazli R, Harirchian MH, Sedighi B, Zamani B, Roudbari A, Razazian N, Khamseh F, Nafissi S
J Neurol Sci 2016 Sep 15;368:35-40. Epub 2016 Jun 25 doi: 10.1016/j.jns.2016.06.056. PMID: 27538598
Marini C, Cistaro A, Campi C, Calvo A, Caponnetto C, Nobili FM, Fania P, Beltrametti MC, Moglia C, Novi G, Buschiazzo A, Perasso A, Canosa A, Scialò C, Pomposelli E, Massone AM, Bagnara MC, Cammarosano S, Bruzzi P, Morbelli S, Sambuceti G, Mancardi G, Piana M, Chiò A
Eur J Nucl Med Mol Imaging 2016 Oct;43(11):2061-71. Epub 2016 Jul 15 doi: 10.1007/s00259-016-3440-3. PMID: 27421971Free PMC Article
Vercruysse P, Sinniger J, El Oussini H, Scekic-Zahirovic J, Dieterlé S, Dengler R, Meyer T, Zierz S, Kassubek J, Fischer W, Dreyhaupt J, Grehl T, Hermann A, Grosskreutz J, Witting A, Van Den Bosch L, Spreux-Varoquaux O; GERP ALS Study Group., Ludolph AC, Dupuis L
Brain 2016 Apr;139(Pt 4):1106-22. Epub 2016 Mar 16 doi: 10.1093/brain/aww004. PMID: 26984187
Fukunaga K, Shinoda Y, Tagashira H
J Pharmacol Sci 2015 Jan;127(1):36-41. Epub 2014 Dec 24 doi: 10.1016/j.jphs.2014.12.012. PMID: 25704016

Prognosis

Fernandes PM, Macleod MR, Bateman A, Abrahams S, Pal S
BMC Neurol 2017 Mar 29;17(1):64. doi: 10.1186/s12883-017-0847-9. PMID: 28356084Free PMC Article
Chen X, Chen Y, Wei Q, Ou R, Cao B, Zhao B, Shang HF
BMC Neurol 2016 Sep 15;16:173. doi: 10.1186/s12883-016-0689-x. PMID: 27634542Free PMC Article
Vandoorne E, Vrijsen B, Belge C, Testelmans D, Buyse B
Acta Clin Belg 2016 Dec;71(6):389-394. Epub 2016 Apr 26 doi: 10.1080/17843286.2016.1173941. PMID: 27112318
Moura MC, Casulari LA, Carvalho Garbi Novaes MR
Amyotroph Lateral Scler Frontotemporal Degener 2016;17(3-4):275-81. Epub 2016 Feb 5 doi: 10.3109/21678421.2016.1140210. PMID: 26850047
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

Clinical prediction guides

E M, Yu S, Dou J, Jin W, Cai X, Mao Y, Zhu D, Yang R
Neurol Sci 2016 Aug;37(8):1203-8. Epub 2016 Apr 21 doi: 10.1007/s10072-016-2575-0. PMID: 27103621
Vercruysse P, Sinniger J, El Oussini H, Scekic-Zahirovic J, Dieterlé S, Dengler R, Meyer T, Zierz S, Kassubek J, Fischer W, Dreyhaupt J, Grehl T, Hermann A, Grosskreutz J, Witting A, Van Den Bosch L, Spreux-Varoquaux O; GERP ALS Study Group., Ludolph AC, Dupuis L
Brain 2016 Apr;139(Pt 4):1106-22. Epub 2016 Mar 16 doi: 10.1093/brain/aww004. PMID: 26984187
Moisset X, Cornut-Chauvinc C, Clavelou P, Pereira B, Dallel R, Guy N
Palliat Med 2016 May;30(5):486-94. Epub 2015 Aug 12 doi: 10.1177/0269216315600332. PMID: 26269326
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
Freischmidt A, Müller K, Zondler L, Weydt P, Volk AE, Božič AL, Walter M, Bonin M, Mayer B, von Arnim CA, Otto M, Dieterich C, Holzmann K, Andersen PM, Ludolph AC, Danzer KM, Weishaupt JH
Brain 2014 Nov;137(Pt 11):2938-50. Epub 2014 Sep 5 doi: 10.1093/brain/awu249. PMID: 25193138

Recent systematic reviews

E M, Yu S, Dou J, Jin W, Cai X, Mao Y, Zhu D, Yang R
Neurol Sci 2016 Aug;37(8):1203-8. Epub 2016 Apr 21 doi: 10.1007/s10072-016-2575-0. PMID: 27103621
Bourke SC, Steer J
Neurodegener Dis Manag 2016 Apr;6(2):147-60. Epub 2016 Apr 1 doi: 10.2217/nmt-2015-0010. PMID: 27033240
Marin B, Logroscino G, Boumédiene F, Labrunie A, Couratier P, Babron MC, Leutenegger AL, Preux PM, Beghi E
Eur J Epidemiol 2016 Mar;31(3):229-45. Epub 2015 Oct 12 doi: 10.1007/s10654-015-0090-x. PMID: 26458931
Nardone R, Höller Y, Taylor AC, Lochner P, Tezzon F, Golaszewski S, Brigo F, Trinka E
Zoology (Jena) 2016 Feb;119(1):64-73. Epub 2015 Sep 21 doi: 10.1016/j.zool.2015.09.003. PMID: 26432396
Slade A, Stanic S
J Neurol Sci 2015 May 15;352(1-2):34-6. Epub 2015 Feb 11 doi: 10.1016/j.jns.2015.02.008. PMID: 25881952

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