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Leukoencephalopathy with vanishing white matter 5(VWM5)

MedGen UID:
1830483
Concept ID:
C5779973
Disease or Syndrome
Synonyms: Leukoencephalopathy with vanishing white matter 5, with or without ovarian failure; VWM5
 
Gene (location): EIF2B5 (3q27.1)
 
Monarch Initiative: MONDO:0957873
OMIM®: 620315

Definition

Leukoencephalopathy with vanishing white matter-5 (VWM5) is a chronic and progressive autosomal recessive leukoencephalopathy characterized by neurologic deterioration usually beginning in late infancy or early childhood; however, juvenile- and adult-onset cases have been reported. Neurologic signs include cerebellar ataxia, spasticity, and relatively preserved mental abilities. The disease is chronic and progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. Death occurs after a variable period of a few years to a few decades, usually following an episode of fever and coma. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy are diagnostic and show a diffuse abnormality of the cerebral white matter beginning in the presymptomatic stage, with increasing amounts of the abnormal white matter vanishing and being replaced by cerebrospinal fluid; autopsy confirms these findings (summary by Leegwater et al., 2001). Ovarian dysgenesis may be present in affected females (Fogli et al., 2003). For a discussion of genetic heterogeneity of VWM, see 603896. Cree Leukoencephalopathy An infantile leukoencephalopathy among the native Cree and Chippewayan indigenous population in Northern Quebec and Manitoba results from homozygosity for an arg195-to-his (R195H; 603945.0005) mutation in the EIF2B5 gene. These patients have disease onset between 3 and 9 months of age, with death in 100% by 21 months of age. [from OMIM]

Clinical features

From HPO
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Megalencephaly
MedGen UID:
65141
Concept ID:
C0221355
Congenital Abnormality
Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia).
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Dilated third ventricle
MedGen UID:
870494
Concept ID:
C4024941
Finding
An increase in size of the third ventricle.
Decreased CSF asialotransferrin to transferrin ratio
MedGen UID:
1863979
Concept ID:
C5937225
Finding
The concentration of asialotransferrin relative to that of transferrin in the cerebrospinal fluid (CSF) is below the lower limit of normal.

Professional guidelines

PubMed

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
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
van der Knaap MS, Schiffmann R, Mochel F, Wolf NI
Lancet Neurol 2019 Oct;18(10):962-972. Epub 2019 Jul 12 doi: 10.1016/S1474-4422(19)30143-7. PMID: 31307818

Recent clinical studies

Etiology

Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
van der Knaap MS, Schiffmann R, Mochel F, Wolf NI
Lancet Neurol 2019 Oct;18(10):962-972. Epub 2019 Jul 12 doi: 10.1016/S1474-4422(19)30143-7. PMID: 31307818
Lynch DS, Wade C, Paiva ARB, John N, Kinsella JA, Merwick Á, Ahmed RM, Warren JD, Mummery CJ, Schott JM, Fox NC, Houlden H, Adams ME, Davagnanam I, Murphy E, Chataway J
J Neurol Neurosurg Psychiatry 2019 May;90(5):543-554. Epub 2018 Nov 22 doi: 10.1136/jnnp-2018-319481. PMID: 30467211Free PMC Article
Marelli C, Salsano E, Politi LS, Labauge P
J Neurol Neurosurg Psychiatry 2019 Feb;90(2):211-218. Epub 2018 Aug 27 doi: 10.1136/jnnp-2018-318666. PMID: 30150321
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article

Diagnosis

Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
van der Knaap MS, Schiffmann R, Mochel F, Wolf NI
Lancet Neurol 2019 Oct;18(10):962-972. Epub 2019 Jul 12 doi: 10.1016/S1474-4422(19)30143-7. PMID: 31307818
Lynch DS, Wade C, Paiva ARB, John N, Kinsella JA, Merwick Á, Ahmed RM, Warren JD, Mummery CJ, Schott JM, Fox NC, Houlden H, Adams ME, Davagnanam I, Murphy E, Chataway J
J Neurol Neurosurg Psychiatry 2019 May;90(5):543-554. Epub 2018 Nov 22 doi: 10.1136/jnnp-2018-319481. PMID: 30467211Free PMC Article
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article
Sarbu N, Shih RY, Jones RV, Horkayne-Szakaly I, Oleaga L, Smirniotopoulos JG
Radiographics 2016 Sep-Oct;36(5):1426-47. doi: 10.1148/rg.2016160031. PMID: 27618323

Therapy

Manikandan M, Azariah B, Sharma R
J Cancer Res Ther 2023 Oct 1;19(7):2076-2078. Epub 2023 Jan 12 doi: 10.4103/jcrt.jcrt_2165_21. PMID: 38376324
Rost NS, Meschia JF, Gottesman R, Wruck L, Helmer K, Greenberg SM; DISCOVERY Investigators
Stroke 2021 Aug;52(8):e499-e516. Epub 2021 May 27 doi: 10.1161/STROKEAHA.120.031611. PMID: 34039035Free PMC Article
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
Bahar-Fuchs A, Clare L, Woods B
Cochrane Database Syst Rev 2013 Jun 5;2013(6):CD003260. doi: 10.1002/14651858.CD003260.pub2. PMID: 23740535Free PMC Article
Tormoehlen LM
Psychiatr Clin North Am 2013 Jun;36(2):277-92. Epub 2013 Apr 12 doi: 10.1016/j.psc.2013.02.006. PMID: 23688692

Prognosis

van der Knaap MS, Bugiani M, Abbink TEM
Handb Clin Neurol 2024;204:77-94. doi: 10.1016/B978-0-323-99209-1.00015-6. PMID: 39322396
van der Knaap MS, Schiffmann R, Mochel F, Wolf NI
Lancet Neurol 2019 Oct;18(10):962-972. Epub 2019 Jul 12 doi: 10.1016/S1474-4422(19)30143-7. PMID: 31307818
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article
Tormoehlen LM
Psychiatr Clin North Am 2013 Jun;36(2):277-92. Epub 2013 Apr 12 doi: 10.1016/j.psc.2013.02.006. PMID: 23688692
Poll-The BT, Engelen M
Semin Neurol 2012 Feb;32(1):42-50. Epub 2012 Mar 15 doi: 10.1055/s-0032-1306385. PMID: 22422205

Clinical prediction guides

van der Knaap MS, Bugiani M, Abbink TEM
Handb Clin Neurol 2024;204:77-94. doi: 10.1016/B978-0-323-99209-1.00015-6. PMID: 39322396
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
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
Filley CM
Clin Neuropsychol 2016 Aug;30(6):901-12. Epub 2016 Jun 29 doi: 10.1080/13854046.2016.1165805. PMID: 27356088
Mortamais M, Artero S, Ritchie K
Int Rev Psychiatry 2013 Dec;25(6):686-98. doi: 10.3109/09540261.2013.838151. PMID: 24423222Free PMC Article

Recent systematic reviews

Iso-Markku P, Kujala UM, Knittle K, Polet J, Vuoksimaa E, Waller K
Br J Sports Med 2022 Jun;56(12):701-709. Epub 2022 Mar 17 doi: 10.1136/bjsports-2021-104981. PMID: 35301183Free PMC Article
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
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
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
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

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