Laboratory Studies

Arylsulfatase A (ARSA) enzyme activity may be decreased in leukocytes or cultured skin fibroblasts. Cerebral spinal fluid (CSF) protein levels may be increased (although this finding is nonspecific). The range of values of ARSA activity in the CSF has been established empirically for metachromatic leukodystrophy (MLD) in clinical practice.^[30]

Metachromatic leukodystrophy may be distinguished from ARSA pseudodeficiency using one of the following tests:

Urine sulfatide level
Radiolabeled sulfatide fibroblast loading
DNA mutation analysis

Arylsulfatase A activity may be measured to identify carriers and make prenatal diagnoses. This test is available in a few select laboratories. In addition, multiplexed immune-quantification assays have been developed that screen numerous lysosomal proteins. Implementation of this technique in newborn screening (using blood spots) for early identification of lysosomal storage disorders has been shown to be feasible but requires further validation.^[31]

Other Tests

Brain MRI may be performed to identify white matter lesions and atrophy, which are characteristic of metachromatic leukodystrophy but is nonspecific.^[32]

The following procedures may be indicated:

Peripheral nerve biopsy (usually not needed)
Lumbar puncture

Metachromatic granules are found in biopsy specimens from peripheral nerves, the kidney, or the gallbladder. Widespread loss of myelin in the CNS and peripheral nerves may be present.

The following tests may be indicated:

Nerve conduction studies
Neurocognitive, neuropsychological testing, or both

Staging

Table 1. Characteristics of the 4 Forms of Metachromatic Leukodystrophy (Open Table in a new window)

Form	Age at Onset (y)	Inheritance Pattern	Frequency	Neurocognitive Deficit	Progression	Effect of Bone Marrow Transplantation
Late infantile	< 4	Autosomal recessive	Most common	Motor milestones lost, neurocognitive function lost	Death within 5-6 y	Not helpful in symptomatic patients; may halt cognitive deterioration in asymptomatic patients
Early juvenile	4-6	Autosomal recessive	Less common	Motor milestones lost, learning and behavior impaired	Death within 10-15 y	May be beneficial in symptomatic and asymptomatic patients
Late juvenile	6-16	Autosomal recessive	Rare	Personality changes, behavioral changes, dementia, psychoses, decline in school or work performance	Slow	May be beneficial in asymptomatic or mildly symptomatic patients
Adult	>16	Autosomal recessive	Rare	Personality changes, behavioral changes, dementia, psychoses, decline in school or work performance	Slow	May be beneficial in asymptomatic or mildly symptomatic patients

Treatment & Management

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Author

Anna V Blenda, PhD Clinical Associate Professor, Department of Biomedical Sciences, University of South Carolina School of Medicine, Greenville

Anna V Blenda, PhD is a member of the following medical societies: American Association for Cancer Research, American College of Medical Genetics and Genomics, American Society for Microbiology

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.

Chief Editor

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

Luis O Rohena, MD, PhD, FAAP, FACMG 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, The Scientific Research Honor Society, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Robert D Steiner, MD, FAAP, FACMG Professor (Clinical), Department of Pediatrics, University of Wisconsin School of Medicine and Public Health; Editor-in-Chief, Genetics in Medicine; Chief Medical Officer, PreventionGenetics

Robert D Steiner, MD, FAAP, FACMG 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: PreventionGenetics-part of Exact Sciences; Acer Therapeutics; DNARx; Best Doctors; PTC Therapeutics; CTX Alliance; Leadiant' Travere<br/>Received income in an amount equal to or greater than $250 from: Marshfield Clinic; PreventionGenetics-part of Exact Sciences; Acer Therapeutics; PTC Therapeutics; DNARx; Leadiant; Travere.

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.

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.

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 for Blood and Marrow Transplantation, American Society of Pediatric Hematology/Oncology

Disclosure: I own stocks in various pharmaceutical companies. This varies on a given week for: multiple and varies.