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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

Newborn screening of neuromuscular diseases.
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
Recent Advancements in the Diagnosis and Treatment of Leukodystrophies.
Bradbury AM, Ream MA
Semin Pediatr Neurol 2021 Apr;37:100876. Epub 2021 Feb 10 doi: 10.1016/j.spen.2021.100876. PMID: 33892849
Metachromatic leukodystrophy: Disease spectrum and approaches for treatment.
van Rappard DF, Boelens JJ, Wolf NI
Best Pract Res Clin Endocrinol Metab 2015 Mar;29(2):261-73. Epub 2014 Oct 16 doi: 10.1016/j.beem.2014.10.001. PMID: 25987178

Curated

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

Recent clinical studies

Etiology

Gene Therapy of Sphingolipid Metabolic Disorders.
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
Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
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
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
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
Lysosomal storage diseases.
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
Adulthood leukodystrophies.
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: 29302065

Diagnosis

Early recognition of patients with leukodystrophies.
Modesti NB, Evans SH, Jaffe N, Vanderver A, Gavazzi F
Curr Probl Pediatr Adolesc Health Care 2022 Dec;52(12):101311. Epub 2022 Dec 2 doi: 10.1016/j.cppeds.2022.101311. PMID: 36470810
Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
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
Recent Advancements in the Diagnosis and Treatment of Leukodystrophies.
Bradbury AM, Ream MA
Semin Pediatr Neurol 2021 Apr;37:100876. Epub 2021 Feb 10 doi: 10.1016/j.spen.2021.100876. PMID: 33892849
Adult Leukodystrophies: A Step-by-Step Diagnostic Approach.
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
Metachromatic leukodystrophy--an update.
Gieselmann V, Krägeloh-Mann I
Neuropediatrics 2010 Feb;41(1):1-6. Epub 2010 Jun 22 doi: 10.1055/s-0030-1253412. PMID: 20571983

Therapy

Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy.
Al-Saady M, Beerepoot S, Plug BC, Breur M, Galabova H, Pouwels PJW, Boelens JJ, Lindemans C, van Hasselt PM, Matzner U, Vanderver A, Bugiani M, van der Knaap MS, Wolf NI
Ann Clin Transl Neurol 2023 Jul;10(7):1146-1159. Epub 2023 May 22 doi: 10.1002/acn3.51796. PMID: 37212343Free PMC Article
Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
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
Recent Advancements in the Diagnosis and Treatment of Leukodystrophies.
Bradbury AM, Ream MA
Semin Pediatr Neurol 2021 Apr;37:100876. Epub 2021 Feb 10 doi: 10.1016/j.spen.2021.100876. PMID: 33892849
Gene-Based Approaches to Inherited Neurometabolic Diseases.
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
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.
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

Prognosis

Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
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
Lysosomal storage diseases.
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
Adulthood leukodystrophies.
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: 29302065
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.
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
Leukodystrophies.
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

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
Clinical Significance of Diffusion Tensor Imaging in Metachromatic Leukodystrophy.
Amedick LB, Martin P, Beschle J, Strölin M, Wilke M, Wolf N, Pouwels P, Hagberg G, Klose U, Naegele T, Kraegeloh-Mann I, Groeschel S
Neuropediatrics 2023 Aug;54(4):244-252. Epub 2023 Apr 13 doi: 10.1055/a-2073-4178. PMID: 37054976Free PMC Article
Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.
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
Adult Leukodystrophies: A Step-by-Step Diagnostic Approach.
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
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy.
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

Recent systematic reviews

The natural history and burden of illness of metachromatic leukodystrophy: a systematic literature review.
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
A systematic review on the birth prevalence of metachromatic leukodystrophy.
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
A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel.
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
A systematic review and meta-analysis of published cases reveals the natural disease history in multiple sulfatase deficiency.
Schlotawa L, Preiskorn J, Ahrens-Nicklas R, Schiller S, Adang LA, Gärtner J, Friede T
J Inherit Metab Dis 2020 Nov;43(6):1288-1297. Epub 2020 Jul 22 doi: 10.1002/jimd.12282. PMID: 32621519
Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review of the literature.
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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    Practice guidelines

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      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.

    Reviews

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