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Metachromatic leukodystrophy, juvenile type

MedGen UID:
155528
Concept ID:
C0751276
Disease or Syndrome
Synonym: Metachromatic leukodystrophy, juvenile form
SNOMED CT: Juvenile metachromatic leucodystrophy (44359008); Metachromatic leukodystrophy, juvenile type (44359008)
 
Monarch Initiative: MONDO:0009591
OMIM®: 250100; 607574
Orphanet: ORPHA309263

Definition

A subtype of Metachromatic leukodystrophy characterized by progressive psychomotor regression with an onset between 30 months and 16 years of age, often beginning with behavioral abnormalities or deterioration of school performance. Further manifestations are ataxia, gait disturbances, reduced deep tendon reflexes, spasticity, seizures, paralysis, dementia, and loss of speech, vision, and hearing, eventually resulting in complete loss of motor and cognitive skills, and decerebration. The rate of deterioration is variable with possible survival up to the third decade of life. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMetachromatic leukodystrophy, juvenile type
Follow this link to review classifications for Metachromatic leukodystrophy, juvenile type in Orphanet.

Professional guidelines

PubMed

Adang LA, Bonkowsky JL, Boelens JJ, Mallack E, Ahrens-Nicklas R, Bernat JA, Bley A, Burton B, Darling A, Eichler F, Eklund E, Emrick L, Escolar M, Fatemi A, Fraser JL, Gaviglio A, Keller S, Patterson MC, Orchard P, Orthmann-Murphy J, Santoro JD, Schöls L, Sevin C, Srivastava IN, Rajan D, Rubin JP, Van Haren K, Wasserstein M, Zerem A, Fumagalli F, Laugwitz L, Vanderver A
Cytotherapy 2024 Jul;26(7):739-748. Epub 2024 Apr 1 doi: 10.1016/j.jcyt.2024.03.487. PMID: 38613540Free PMC Article
Dangouloff T, Boemer F, Servais L
Neuromuscul Disord 2021 Oct;31(10):1070-1080. Epub 2021 Jul 28 doi: 10.1016/j.nmd.2021.07.008. PMID: 34620514
Batzios SP, Zafeiriou DI
Mol Genet Metab 2012 Jan;105(1):56-63. Epub 2011 Oct 18 doi: 10.1016/j.ymgme.2011.10.002. PMID: 22078456

Curated

Leukodystrophies in Children: Diagnosis, Care, and Treatment, Pediatrics (2021) 148 (3): e2021053126.

Recent clinical studies

Etiology

Shaimardanova AA, Solovyeva VV, Issa SS, Rizvanov AA
Int J Mol Sci 2023 Feb 11;24(4) doi: 10.3390/ijms24043627. PMID: 36835039Free PMC Article
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
Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ
Nat Rev Dis Primers 2018 Oct 1;4(1):27. doi: 10.1038/s41572-018-0025-4. PMID: 30275469
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
Perlman SJ, Mar S
Adv Exp Med Biol 2012;724:154-71. doi: 10.1007/978-1-4614-0653-2_13. PMID: 22411242

Diagnosis

Adang LA, Bonkowsky JL, Boelens JJ, Mallack E, Ahrens-Nicklas R, Bernat JA, Bley A, Burton B, Darling A, Eichler F, Eklund E, Emrick L, Escolar M, Fatemi A, Fraser JL, Gaviglio A, Keller S, Patterson MC, Orchard P, Orthmann-Murphy J, Santoro JD, Schöls L, Sevin C, Srivastava IN, Rajan D, Rubin JP, Van Haren K, Wasserstein M, Zerem A, Fumagalli F, Laugwitz L, Vanderver A
Cytotherapy 2024 Jul;26(7):739-748. Epub 2024 Apr 1 doi: 10.1016/j.jcyt.2024.03.487. PMID: 38613540Free PMC Article
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
Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A
Lancet 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785Free PMC Article
Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT
Radiographics 2019 Jan-Feb;39(1):153-168. doi: 10.1148/rg.2019180081. PMID: 30620693
Cesani M, Lorioli L, Grossi S, Amico G, Fumagalli F, Spiga I, Filocamo M, Biffi A
Hum Mutat 2016 Jan;37(1):16-27. Epub 2015 Nov 4 doi: 10.1002/humu.22919. PMID: 26462614

Therapy

Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A
Lancet 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785Free PMC Article
Bradbury AM, Ream MA
Semin Pediatr Neurol 2021 Apr;37:100876. Epub 2021 Feb 10 doi: 10.1016/j.spen.2021.100876. PMID: 33892849
Poletti V, Biffi A
Hum Gene Ther 2019 Oct;30(10):1222-1235. Epub 2019 Sep 10 doi: 10.1089/hum.2019.190. PMID: 31397176
Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, Naldini L
Science 2013 Aug 23;341(6148):1233158. Epub 2013 Jul 11 doi: 10.1126/science.1233158. PMID: 23845948
Matzner U, Gieselmann V
Expert Opin Biol Ther 2005 Jan;5(1):55-65. doi: 10.1517/14712598.5.1.55. PMID: 15709909

Prognosis

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
Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A
Lancet 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785Free PMC Article
Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ
Nat Rev Dis Primers 2018 Oct 1;4(1):27. doi: 10.1038/s41572-018-0025-4. PMID: 30275469
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
Perlman SJ, Mar S
Adv Exp Med Biol 2012;724:154-71. doi: 10.1007/978-1-4614-0653-2_13. PMID: 22411242

Clinical prediction guides

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
Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A
Lancet 2022 Jan 22;399(10322):372-383. doi: 10.1016/S0140-6736(21)02017-1. PMID: 35065785Free PMC Article
Resende LL, de Paiva ARB, Kok F, da Costa Leite C, Lucato LT
Radiographics 2019 Jan-Feb;39(1):153-168. doi: 10.1148/rg.2019180081. PMID: 30620693
Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, Naldini L
Science 2013 Aug 23;341(6148):1233158. Epub 2013 Jul 11 doi: 10.1126/science.1233158. PMID: 23845948
Batzios SP, Zafeiriou DI
Mol Genet Metab 2012 Jan;105(1):56-63. Epub 2011 Oct 18 doi: 10.1016/j.ymgme.2011.10.002. PMID: 22078456

Recent systematic reviews

Chang SC, Eichinger CS, Field P
Eur J Med Res 2024 Mar 18;29(1):181. doi: 10.1186/s40001-024-01771-1. PMID: 38494502Free PMC Article
Chang SC, Bergamasco A, Bonnin M, Bisonó TA, Moride Y
Orphanet J Rare Dis 2024 Feb 21;19(1):80. doi: 10.1186/s13023-024-03044-w. PMID: 38383398Free PMC Article
Armstrong N, Olaye A, Noake C, Pang F
Orphanet J Rare Dis 2023 Aug 29;18(1):248. doi: 10.1186/s13023-023-02814-2. PMID: 37644601Free PMC Article
Musolino PL, Lund TC, Pan J, Escolar ML, Paker AM, Duncan CN, Eichler FS
Neuropediatrics 2014 Jun;45(3):169-74. Epub 2014 Jan 23 doi: 10.1055/s-0033-1364179. PMID: 24459069Free PMC Article
Mahmood A, Berry J, Wenger DA, Escolar M, Sobeih M, Raymond G, Eichler FS
J Child Neurol 2010 May;25(5):572-80. Epub 2009 Dec 28 doi: 10.1177/0883073809341669. PMID: 20038527Free PMC Article

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Table of contents

    Genetic Testing Registry

    Clinical resources

    Practice guidelines

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      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • AAP, 2021
      Leukodystrophies in Children: Diagnosis, Care, and Treatment, Pediatrics (2021) 148 (3): e2021053126.

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