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Leukoencephalopathy with vanishing white matter 3(VWM3)

MedGen UID:
1841041
•Concept ID:
C5830405
•
Disease or Syndrome
Synonyms: Leukoencephalopathy with vanishing white matter 3, with or without ovarian failure; VWM3
 
Gene (location): EIF2B3 (1p34.1)
 
Monarch Initiative: MONDO:0957871
OMIM®: 620313

Definition

Leukoencephalopathy with vanishing white matter-3 (VWM3) is an autosomal recessive leukoencephalopathy characterized by progressive cerebellar ataxia, spasticity, and mental decline. The course is chronic and progressive, with episodes of rapid deterioration following minor head trauma. Affected females may have amenorrhea. Magnetic resonance imaging (MRI) reveals diffuse leukoencephalopathy with lesions having cerebrospinal fluid (CSF)-like signals (summary by Matsukawa et al., 2011). For a discussion of genetic heterogeneity of VWM, see 603896. [from OMIM]

Clinical features

From HPO
Secondary amenorrhea
MedGen UID:
115919
•Concept ID:
C0232940
•
Disease or Syndrome
The cessation of menstruation for six months or more in a female that is not pregnant, breastfeeding or menopausal.
See: Feature record | Search on this feature
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
Dysarthria
MedGen UID:
8510
•Concept ID:
C0013362
•
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
See: Feature record | Search on this feature
Seizure
MedGen UID:
20693
•Concept ID:
C0036572
•
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
See: Feature record | Search on this feature
Leukoencephalopathy
MedGen UID:
78722
•Concept ID:
C0270612
•
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
See: Feature record | Search on this feature
Loss of ambulation
MedGen UID:
332305
•Concept ID:
C1836843
•
Finding
Inability to walk in a person who previous had the ability to walk.
See: Feature record | Search on this feature
Hemianopia
MedGen UID:
9193
•Concept ID:
C0018979
•
Finding
Partial or complete loss of vision in one half of the visual field of one or both eyes.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Posterior reversible encephalopathy syndrome (PRES): diagnosis and management.
Triplett JD, Kutlubaev MA, Kermode AG, Hardy T
Pract Neurol 2022 Jun;22(3):183-189. Epub 2022 Jan 19 doi: 10.1136/practneurol-2021-003194. PMID: 35046115
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
Monoclonal Gammopathy-Associated Peripheral Neuropathy: Diagnosis and Management.
Chaudhry HM, Mauermann ML, Rajkumar SV
Mayo Clin Proc 2017 May;92(5):838-850. doi: 10.1016/j.mayocp.2017.02.003. PMID: 28473042Free PMC Article

Recent clinical studies

Etiology

Progressive Multifocal Leukoencephalopathy: Pathogenesis, Diagnostic Tools, and Potential Biomarkers of Response to Therapy.
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Neurology 2023 Oct 17;101(16):700-713. Epub 2023 Jul 24 doi: 10.1212/WNL.0000000000207622. PMID: 37487750Free PMC Article
Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.
Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS
JAMA Neurol 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122. PMID: 30422209Free PMC Article
Vascular Cognitive Impairment.
Dichgans M, Leys D
Circ Res 2017 Feb 3;120(3):573-591. doi: 10.1161/CIRCRESAHA.116.308426. PMID: 28154105
Vascular cognitive impairment and dementia.
Gorelick PB, Counts SE, Nyenhuis D
Biochim Biophys Acta 2016 May;1862(5):860-8. Epub 2015 Dec 15 doi: 10.1016/j.bbadis.2015.12.015. PMID: 26704177Free PMC Article
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Diagnosis

Acute disseminated encephalomyelitis.
Clare E
JAAPA 2022 Sep 1;35(9):32-35. doi: 10.1097/01.JAA.0000832604.33045.9d. PMID: 36007116
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
Alexander Disease.
Tavasoli A, Armangue T, Ho CY, Whitehead M, Bornhorst M, Rhee J, Hwang EI, Wells EM, Packer R, van der Knaap MS, Bugiani M, Vanderver A
J Child Neurol 2017 Feb;32(2):184-187. Epub 2016 Oct 10 doi: 10.1177/0883073816673263. PMID: 28112050
Acute Disseminated Encephalomyelitis.
J Clin Apher 2016 Jun;31(3):163-202. doi: 10.1002/jca.21474. PMID: 27322219
Toxic leukoencephalopathies.
Tormoehlen LM
Neurol Clin 2011 Aug;29(3):591-605. doi: 10.1016/j.ncl.2011.05.005. PMID: 21803212

Therapy

Posterior reversible encephalopathy syndrome (PRES): diagnosis and management.
Triplett JD, Kutlubaev MA, Kermode AG, Hardy T
Pract Neurol 2022 Jun;22(3):183-189. Epub 2022 Jan 19 doi: 10.1136/practneurol-2021-003194. PMID: 35046115
Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.
Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ
Cochrane Database Syst Rev 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2. PMID: 34918337Free PMC Article
Cannabinoids for the treatment of dementia.
Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L
Cochrane Database Syst Rev 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2. PMID: 34532852Free PMC Article
Memantine for dementia.
McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J
Cochrane Database Syst Rev 2019 Mar 20;3(3):CD003154. doi: 10.1002/14651858.CD003154.pub6. PMID: 30891742Free PMC Article
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Prognosis

Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis.
Rindi LV, Zaçe D, Braccialarghe N, Massa B, Barchi V, Iannazzo R, Fato I, De Maria F, Kontogiannis D, Malagnino V, Sarmati L, Iannetta M
Drug Saf 2024 Apr;47(4):333-354. Epub 2024 Feb 7 doi: 10.1007/s40264-023-01383-4. PMID: 38321317
Acute disseminated encephalomyelitis.
Clare E
JAAPA 2022 Sep 1;35(9):32-35. doi: 10.1097/01.JAA.0000832604.33045.9d. PMID: 36007116
Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.
Wang CX
Paediatr Drugs 2021 May;23(3):213-221. Epub 2021 Apr 8 doi: 10.1007/s40272-021-00441-7. PMID: 33830467Free PMC Article
Natural History of Vanishing White Matter.
Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM, Lourenço CM, Naidu S, Mierzewska H, Gemke RJBJ, de Vet HCW, Uitdehaag BMJ, Lissenberg-Witte BI; VWM Research Group, van der Knaap MS
Ann Neurol 2018 Aug;84(2):274-288. Epub 2018 Sep 6 doi: 10.1002/ana.25287. PMID: 30014503Free PMC Article
Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.
Bhojwani D, Sabin ND, Pei D, Yang JJ, Khan RB, Panetta JC, Krull KR, Inaba H, Rubnitz JE, Metzger ML, Howard SC, Ribeiro RC, Cheng C, Reddick WE, Jeha S, Sandlund JT, Evans WE, Pui CH, Relling MV
J Clin Oncol 2014 Mar 20;32(9):949-59. Epub 2014 Feb 18 doi: 10.1200/JCO.2013.53.0808. PMID: 24550419Free PMC Article

Clinical prediction guides

Predicting disease severity in metachromatic leukodystrophy using protein activity and a patient phenotype matrix.
Trinidad M, Hong X, Froelich S, Daiker J, Sacco J, Nguyen HP, Campagna M, Suhr D, Suhr T, LeBowitz JH, Gelb MH, Clark WT
Genome Biol 2023 Jul 21;24(1):172. doi: 10.1186/s13059-023-03001-z. PMID: 37480112Free PMC Article
Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum.
Crow YJ, Marshall H, Rice GI, Seabra L, Jenkinson EM, Baranano K, Battini R, Berger A, Blair E, Blauwblomme T, Bolduc F, Boddaert N, Buckard J, Burnett H, Calvert S, Caumes R, Ng AC, Chiang D, Clifford DB, Cordelli DM, de Burca A, Demic N, Desguerre I, De Waele L, Di Fonzo A, Dunham SR, Dyack S, Elmslie F, Ferrand M, Fisher G, Karimiani EG, Ghoumid J, Gibbon F, Goel H, Hilmarsen HT, Hughes I, Jacob A, Jones EA, Kumar R, Leventer RJ, MacDonald S, Maroofian R, Mehta SG, Metz I, Monfrini E, Neumann D, Noetzel M, O'Driscoll M, Õunap K, Panzer A, Parikh S, Prabhakar P, Ramond F, Sandford R, Saneto R, Soh C, Stutterd CA, Subramanian GM, Talbot K, Thomas RH, Toro C, Touraine R, Wakeling E, Wassmer E, Whitney A, Livingston JH, O'Keefe RT, Badrock AP
Am J Med Genet A 2021 Jan;185(1):15-25. Epub 2020 Oct 7 doi: 10.1002/ajmg.a.61907. PMID: 33029936
Clinical Significance of Magnetic Resonance Imaging Markers of Vascular Brain Injury: A Systematic Review and Meta-analysis.
Debette S, Schilling S, Duperron MG, Larsson SC, Markus HS
JAMA Neurol 2019 Jan 1;76(1):81-94. doi: 10.1001/jamaneurol.2018.3122. PMID: 30422209Free PMC Article
Natural History of Vanishing White Matter.
Hamilton EMC, van der Lei HDW, Vermeulen G, Gerver JAM, Lourenço CM, Naidu S, Mierzewska H, Gemke RJBJ, de Vet HCW, Uitdehaag BMJ, Lissenberg-Witte BI; VWM Research Group, van der Knaap MS
Ann Neurol 2018 Aug;84(2):274-288. Epub 2018 Sep 6 doi: 10.1002/ana.25287. PMID: 30014503Free PMC Article
Newborn screening for Krabbe disease in New York State: the first eight years' experience.
Orsini JJ, Kay DM, Saavedra-Matiz CA, Wenger DA, Duffner PK, Erbe RW, Biski C, Martin M, Krein LM, Nichols M, Kurtzberg J, Escolar ML, Adams DJ, Arnold GL, Iglesias A, Galvin-Parton P, Kronn DF, Kwon JM, Levy PA, Pellegrino JE, Shur N, Wasserstein MP, Caggana M; New York State Krabbe Disease Consortium
Genet Med 2016 Mar;18(3):239-48. Epub 2016 Jan 21 doi: 10.1038/gim.2015.211. PMID: 26795590

Recent systematic reviews

Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.
Mühlbauer V, Möhler R, Dichter MN, Zuidema SU, Köpke S, Luijendijk HJ
Cochrane Database Syst Rev 2021 Dec 17;12(12):CD013304. doi: 10.1002/14651858.CD013304.pub2. PMID: 34918337Free PMC Article
Cannabinoids for the treatment of dementia.
Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L
Cochrane Database Syst Rev 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2. PMID: 34532852Free PMC Article
The Prevalence of Dementia: A Systematic Review and Meta-Analysis.
Cao Q, Tan CC, Xu W, Hu H, Cao XP, Dong Q, Tan L, Yu JT
J Alzheimers Dis 2020;73(3):1157-1166. doi: 10.3233/JAD-191092. PMID: 31884487
Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies.
Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd
Br J Psychiatry 2013 May;202(5):329-35. doi: 10.1192/bjp.bp.112.118307. PMID: 23637108Free PMC Article
The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.
Debette S, Markus HS
BMJ 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666. PMID: 20660506Free PMC Article

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