History

Features of symptoms found in patients with each of the 4 forms of metachromatic leukodystrophy (MLD) are provided in the following lists.

1. The infantile form includes the following:

Gait disturbances
Memory deficits
Seizures (may be present)
Loss of motor developmental milestones
Decreased attention span
Speech disturbances
Decline in school performance

2. The early juvenile form includes the following:

Gait disturbances
Tremors
Clumsiness
Loss of previously achieved skills
Intellectual decline
Behavioral changes
Seizures (possible)

3. The late juvenile and adult forms include the following:

Decreased work or school performance
Behavioral changes
Memory loss
Seizures (may be present)
Psychoses
Gradual loss of motor skills

A study by Harrington and colleagues^[25] confirmed clear overall differences in symptom profiles and overall disease progression related to late infantile and juvenile MLD; however, each subtype was characterized by some variability among individuals.

Physical

Neurodevelopmental tests demonstrate the following findings in patients with infantile or early juvenile metachromatic leukodystrophy (MLD):

Loss of previously achieved developmental milestones
Tremors
Truncal ataxia
Hyperreflexia progressing to hyporeflexia
Hypotonia
Gait abnormalities
Optic atrophy

Neurocognitive tests demonstrate the following abnormalities in patients with late juvenile or adult MLD:

Dementia
Memory loss
Disinhibition
Impulsiveness
Decreased motor function
Optic atrophy

Differential Diagnoses

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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.

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

Metachromatic Leukodystrophy Clinical Presentation

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