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Metachromatic Leukodystrophy Differential Diagnoses

  • Author: Alan K Ikeda, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Aug 21, 2014
 
 

Diagnostic Considerations

As many as 1-2% of people may have low (5-15%) or reference range levels of arylsulfatase A in the serum, but sulfatide is not stored. These individuals are usually healthy and asymptomatic. The presence of normal urinary sulfatide levels (elevated in patients with metachromatic leukodystrophy [MLD]) distinguishes arylsulfatase A pseudodeficiency from metachromatic leukodystrophy. Arylsulfatase A pseudodeficiency may also be distinguished using gene mutation analysis or an evaluation of radiolabeled sulfatide fibroblast uptake and accumulation.

Other problems to consider include the following:

  • Schizophrenia
  • Antisocial personality disorder
  • X-linked adrenoleukodystrophy
  • Multiple sulfatase deficiency

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Alan K Ikeda, MD Interim Medical Director, Director of Oncology, Children's Specialty Center of Las Vegas

Alan K Ikeda, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, American Society for Blood and Marrow Transplantation

Disclosure: Nothing to disclose.

Coauthor(s)

Robert D Steiner, MD Chief Medical Officer, Acer Therapeutics; Clinical Professor, University of Wisconsin School of Medicine and Public Health

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Acer Therapeutics; Retrophin; Raptor Pharma; Veritas Genetics; Censa Pharma<br/>Received income in an amount equal to or greater than $250 from: Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma.

Theodore Moore, MD, MS Professor and Chief, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Director of Pediatric Blood and Marrow Transplant Program, University of California, Los Angeles, David Geffen School of Medicine

Theodore Moore, MD, MS is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, Society for Pediatric Research, American Society for Blood and Marrow Transplantation, Western Society for Pediatric Research, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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  2. Anlar B, Waye JS, Eng B. Atypical clinical course in juvenile metachromatic leukodystrophy involving novel arylsulfatase A gene mutations. Dev Med Child Neurol. 2006 May. 48(5):383-7. [Medline].

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  8. Krivit W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immun. 2004. 26:119-132. [Medline].

  9. Martin PL, Carter SL, Kernan NA. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006 Feb. 12(2):184-94. [Medline].

  10. Consiglio A, Quattrini A, Martino S, et al. In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Nat Med. 2001 Mar. 7(3):310-6. [Medline].

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  12. Kawabata K, Migita M, Mochizuki H. Ex vivo cell-mediated gene therapy for metachromatic leukodystrophy using neurospheres. Brain Res. 2006 Jun 13. 1094(1):13-23. [Medline].

  13. Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013 Aug 23. 341(6148):1233158. [Medline].

  14. Matzner U, Herbst E, Hedayati K, et al. Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum Mol Genet. 2005 May. 14(9):1139-1152. [Medline].

  15. Givogri MI, Galbiati F, Fasano S. Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy. J Neurosci. 2006 Mar 22. 26(12):3109-19. [Medline].

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Table 1. Characteristics of the 4 Forms of Metachromatic Leukodystrophy
FormAge at



Onset



(y)



Inheritance



Pattern



FrequencyNeurocognitive



Deficit



ProgressionEffect of Bone



Marrow



Transplantation



Late infantile< 4Autosomal



recessive



Most commonMotor milestones lost,



neurocognitive functions lost



Death within 5-6 yNot helpful in



symptomatic patients;



may halt cognitive



deterioration in



asymptomatic patients



Early juvenile4-6Autosomal



recessive



Less commonMotor milestones lost,



learning and behavior



impaired



Death within



10-15 y



May be beneficial in symptomatic and asymptomatic patients
Late juvenile6-16Autosomal



recessive



RarePersonality changes,



behavioral changes,



dementia, psychoses,



decreased school or



work performance



SlowMay be beneficial in asymptomatic or mildly symptomatic patients
Adult>16Autosomal



recessive



RarePersonality changes,



behavioral changes,



dementia, psychoses,



decreased school or



work performance



SlowMay be beneficial in asymptomatic or mildly symptomatic patients
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