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Metachromatic leukodystrophy, late infantile form

MedGen UID:
155529
•Concept ID:
C0751278
•
Disease or Syndrome
Synonym: Metachromatic leukodystrophy, late infantile
SNOMED CT: Late infantile metachromatic leucodystrophy (47683004); Greenfield disease (47683004); Metachromatic leukodystrophy, congenital type (40802007); Metachromatic leukodystrophy, late infantile type (47683004)
 
Monarch Initiative: MONDO:0017729
OMIM®: 250100; 607574
Orphanet: ORPHA309256

Definition

A subtype of Metachromatic leukodystrophy characterized by rapidly progressive psychomotor regression with an onset before 30 months of age after a period of apparently normal development. Manifestations developing during the course of the disease are impaired feeding and swallowing due to pseudobulbar palsies, seizures, painful spasms, muscle weakness, ataxia, paralysis, dementia, and loss of speech, vision, and hearing, quickly resulting in complete loss of motor and cognitive skills, and decerebration. Death occurs within the first decade of life. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMetachromatic leukodystrophy, late infantile form

Professional guidelines

PubMed

Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.
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
Complex genotypes in family with metachromatic leukodystrophy: Effect of trans and cis mutations distribution on the phenotype variability.
Ben Issa A, Kamoun F, Bouchaala W, Charfi Triki C, Fakhfakh F
Int J Dev Neurosci 2024 Feb;84(1):35-46. Epub 2023 Oct 17 doi: 10.1002/jdn.10306. PMID: 37848385
Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships?
Baumann N, Turpin JC, Lefevre M, Colsch B
J Physiol Paris 2002 Apr-Jun;96(3-4):301-6. doi: 10.1016/s0928-4257(02)00019-0. PMID: 12445909

Curated

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

Recent clinical studies

Etiology

Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.
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
Insights into the natural history of metachromatic leukodystrophy from interviews with caregivers.
Harrington M, Whalley D, Twiss J, Rushton R, Martin S, Huynh L, Yang H
Orphanet J Rare Dis 2019 Apr 29;14(1):89. doi: 10.1186/s13023-019-1060-2. PMID: 31036045Free PMC Article
Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course.
Groeschel S, Kehrer C, Engel C, I Dali C, Bley A, Steinfeld R, Grodd W, Krägeloh-Mann I
J Inherit Metab Dis 2011 Oct;34(5):1095-102. Epub 2011 Jun 23 doi: 10.1007/s10545-011-9361-1. PMID: 21698385
Clinical and biochemical study of 29 Brazilian patients with metachromatic leukodystrophy.
Artigalás O, Lagranha VL, Saraiva-Pereira ML, Burin MG, Lourenço CM, van der Linden H Jr, Santos ML, Rosemberg S, Steiner CE, Kok F, de Souza CF, Jardim LB, Giugliani R, Schwartz IV
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S257-62. Epub 2010 Jul 2 doi: 10.1007/s10545-010-9140-4. PMID: 20596894
The cerebral lipidoses.
Malone MJ
Pediatr Clin North Am 1976 May;23(2):303-26. doi: 10.1016/s0031-3955(16)33273-4. PMID: 818606

Diagnosis

Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.
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
T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy.
Martin P, Hagberg GE, Schultz T, Harzer K, Klose U, Bender B, Nägele T, Scheffler K, Krägeloh-Mann I, Groeschel S
Clin Neuroradiol 2021 Dec;31(4):969-980. Epub 2020 Nov 23 doi: 10.1007/s00062-020-00975-2. PMID: 33226437Free PMC Article
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
Molecular genetics of metachromatic leukodystrophy.
Gieselmann V, Polten A, Kreysing J, von Figura K
J Inherit Metab Dis 1994;17(4):500-9. doi: 10.1007/BF00711364. PMID: 7967499
The cerebral lipidoses.
Malone MJ
Pediatr Clin North Am 1976 May;23(2):303-26. doi: 10.1016/s0031-3955(16)33273-4. PMID: 818606

Therapy

Acute-onset paralytic strabismus in toddlers is important to consider as a potential early sign of late-infantile Metachromatic Leukodystrophy.
Beerepoot S, Wolf NI, Wehner K, Bender B, van der Knaap MS, Krägeloh-Mann I, Groeschel S
Eur J Paediatr Neurol 2022 Mar;37:87-93. Epub 2022 Feb 3 doi: 10.1016/j.ejpn.2022.01.020. PMID: 35152000
Phenotypic variation between siblings with Metachromatic Leukodystrophy.
Elgün S, Waibel J, Kehrer C, van Rappard D, Böhringer J, Beck-Wödl S, Just J, Schöls L, Wolf N, Krägeloh-Mann I, Groeschel S
Orphanet J Rare Dis 2019 Jun 11;14(1):136. doi: 10.1186/s13023-019-1113-6. PMID: 31186049Free PMC Article
Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy.
Martin HR, Poe MD, Provenzale JM, Kurtzberg J, Mendizabal A, Escolar ML
Biol Blood Marrow Transplant 2013 Apr;19(4):616-24. Epub 2013 Jan 22 doi: 10.1016/j.bbmt.2013.01.010. PMID: 23348427
The natural course of gross motor deterioration in metachromatic leukodystrophy.
Kehrer C, Blumenstock G, Gieselmann V, Krägeloh-Mann I; GERMAN LEUKONET
Dev Med Child Neurol 2011 Sep;53(9):850-855. Epub 2011 Jun 27 doi: 10.1111/j.1469-8749.2011.04028.x. PMID: 21707604
Intracerebral adeno-associated virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy.
Sevin C, Benraiss A, Van Dam D, Bonnin D, Nagels G, Verot L, Laurendeau I, Vidaud M, Gieselmann V, Vanier M, De Deyn PP, Aubourg P, Cartier N
Hum Mol Genet 2006 Jan 1;15(1):53-64. Epub 2005 Nov 25 doi: 10.1093/hmg/ddi425. PMID: 16311251

Prognosis

Longitudinal Characterization of the Clinical Course of Intermediate-Severe Salla Disease.
Chapleau A, Mirchi A, Tran LT, Poulin C, Bernard G
Pediatr Neurol 2023 Nov;148:133-137. Epub 2023 Aug 19 doi: 10.1016/j.pediatrneurol.2023.08.013. PMID: 37713976
T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy.
Martin P, Hagberg GE, Schultz T, Harzer K, Klose U, Bender B, Nägele T, Scheffler K, Krägeloh-Mann I, Groeschel S
Clin Neuroradiol 2021 Dec;31(4):969-980. Epub 2020 Nov 23 doi: 10.1007/s00062-020-00975-2. PMID: 33226437Free PMC Article
Phenotypic variation between siblings with Metachromatic Leukodystrophy.
Elgün S, Waibel J, Kehrer C, van Rappard D, Böhringer J, Beck-Wödl S, Just J, Schöls L, Wolf N, Krägeloh-Mann I, Groeschel S
Orphanet J Rare Dis 2019 Jun 11;14(1):136. doi: 10.1186/s13023-019-1113-6. PMID: 31186049Free PMC Article
Clinical and biochemical study of 29 Brazilian patients with metachromatic leukodystrophy.
Artigalás O, Lagranha VL, Saraiva-Pereira ML, Burin MG, Lourenço CM, van der Linden H Jr, Santos ML, Rosemberg S, Steiner CE, Kok F, de Souza CF, Jardim LB, Giugliani R, Schwartz IV
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S257-62. Epub 2010 Jul 2 doi: 10.1007/s10545-010-9140-4. PMID: 20596894
The cerebral lipidoses.
Malone MJ
Pediatr Clin North Am 1976 May;23(2):303-26. doi: 10.1016/s0031-3955(16)33273-4. PMID: 818606

Clinical prediction guides

Complex genotypes in family with metachromatic leukodystrophy: Effect of trans and cis mutations distribution on the phenotype variability.
Ben Issa A, Kamoun F, Bouchaala W, Charfi Triki C, Fakhfakh F
Int J Dev Neurosci 2024 Feb;84(1):35-46. Epub 2023 Oct 17 doi: 10.1002/jdn.10306. PMID: 37848385
Longitudinal Characterization of the Clinical Course of Intermediate-Severe Salla Disease.
Chapleau A, Mirchi A, Tran LT, Poulin C, Bernard G
Pediatr Neurol 2023 Nov;148:133-137. Epub 2023 Aug 19 doi: 10.1016/j.pediatrneurol.2023.08.013. PMID: 37713976
Acute-onset paralytic strabismus in toddlers is important to consider as a potential early sign of late-infantile Metachromatic Leukodystrophy.
Beerepoot S, Wolf NI, Wehner K, Bender B, van der Knaap MS, Krägeloh-Mann I, Groeschel S
Eur J Paediatr Neurol 2022 Mar;37:87-93. Epub 2022 Feb 3 doi: 10.1016/j.ejpn.2022.01.020. PMID: 35152000
Metachromatic leukodystrophy: natural course of cerebral MRI changes in relation to clinical course.
Groeschel S, Kehrer C, Engel C, I Dali C, Bley A, Steinfeld R, Grodd W, Krägeloh-Mann I
J Inherit Metab Dis 2011 Oct;34(5):1095-102. Epub 2011 Jun 23 doi: 10.1007/s10545-011-9361-1. PMID: 21698385
Clinical and biochemical study of 29 Brazilian patients with metachromatic leukodystrophy.
Artigalás O, Lagranha VL, Saraiva-Pereira ML, Burin MG, Lourenço CM, van der Linden H Jr, Santos ML, Rosemberg S, Steiner CE, Kok F, de Souza CF, Jardim LB, Giugliani R, Schwartz IV
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S257-62. Epub 2010 Jul 2 doi: 10.1007/s10545-010-9140-4. PMID: 20596894

Recent systematic reviews

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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    Curated

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

    Reviews

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