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Metachromatic leukodystrophy, adult type

MedGen UID:
199625
•Concept ID:
C0751279
•
Disease or Syndrome
Synonym: Metachromatic leukodystrophy, adult form
SNOMED CT: Adult metachromatic leucodystrophy (24326000); Adult metachromatic leukodystrophy (24326000); Metachromatic leukodystrophy, adult type (24326000)
 
Monarch Initiative: MONDO:0017730
OMIM®: 250100; 607574
Orphanet: ORPHA309271

Definition

A subtype of Metachromatic leukodystrophy characterized by progressive psychomotor regression with an insidious onset after the age of 16 years, most often beginning with intellectual and behavioral changes, such as memory deficits or emotional instability. The clinical picture is dominated by gradual cognitive, later also motor, decline, taking a protracted course with periods of waxing and waning. Decerebration and death occur within decades after disease onset. [from ORDO]

Term Hierarchy

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

Professional guidelines

PubMed

Newborn screening in metachromatic leukodystrophy - European consensus-based recommendations on clinical management.
Laugwitz L, Schoenmakers DH, Adang LA, Beck-Woedl S, Bergner C, Bernard G, Bley A, Boyer A, Calbi V, Dekker H, Eichler F, Eklund E, Fumagalli F, Gavazzi F, Grønborg SW, van Hasselt P, Langeveld M, Lindemans C, Mochel F, Oberg A, Ram D, Saunier-Vivar E, Schöls L, Scholz M, Sevin C, Zerem A, Wolf NI, Groeschel S
Eur J Paediatr Neurol 2024 Mar;49:141-154. Epub 2024 Mar 9 doi: 10.1016/j.ejpn.2024.03.003. PMID: 38554683
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
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 clinical studies

Etiology

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
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
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: 29302065Free PMC Article

Diagnosis

Leukodystrophy Imaging: Insights for Diagnostic Dilemmas.
Thakkar RN, Patel D, Kioutchoukova IP, Al-Bahou R, Reddy P, Foster DT, Lucke-Wold B
Med Sci (Basel) 2024 Jan 25;12(1) doi: 10.3390/medsci12010007. PMID: 38390857Free PMC Article
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
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
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

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
Gene therapy of metachromatic leukodystrophy.
Matzner U, Gieselmann V
Expert Opin Biol Ther 2005 Jan;5(1):55-65. doi: 10.1517/14712598.5.1.55. PMID: 15709909

Prognosis

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
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: 29302065Free PMC Article
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

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
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
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

Experiences of patients with metachromatic leukodystrophy, adrenoleukodystrophy, or Krabbe disease and the experiences of their family members: a qualitative systematic review.
Koto Y, Ueki S, Yamakawa M, Sakai N
JBI Evid Synth 2024 Jul 1;22(7):1262-1302. doi: 10.11124/JBIES-23-00303. PMID: 38533650Free PMC Article
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
Hematopoietic stem cell transplantation in the leukodystrophies: a systematic review of the literature.
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

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