Metachromatic leukodystrophy

Información en español Title

Other Names:

Leukodystrophy metachromatic; Metachromatic leukoencephalopathy; MLD; Leukodystrophy metachromatic; Metachromatic leukoencephalopathy; MLD; Sulfatide lipidosis; Arylsulfatase A deficiency; Cerebral sclerosis diffuse metachromatic form; Cerebroside sulfatase deficiency; ARSA deficiency See More

Categories:

Metabolic disorders

Summary Summary

Metachromatic leukodystrophy is an inherited condition characterized by the accumulation of fats called sulfatides in cells, especially cells of the nervous system. This accumulation results in progressive destruction of white matter of the brain, which consists of nerve fibers covered by myelin. Affected individuals experience progressive deterioration of intellectual functions and motor skills, such as the ability to walk. They also develop loss of sensation in the extremities, incontinence, seizures, paralysis, inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. This condition is inherited in an autosomal recessive pattern and is caused by mutations in the ARSA and PSAP genes.^[1]

Last updated: 9/19/2014

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Ataxia	Very frequent (present in 80%-99% of cases)
Behavioral abnormality	Very frequent (present in 80%-99% of cases)
Coma	Very frequent (present in 80%-99% of cases)
Decreased nerve conduction velocity	Very frequent (present in 80%-99% of cases)
Developmental regression	Very frequent (present in 80%-99% of cases)
Gait disturbance	Very frequent (present in 80%-99% of cases)
Genu recurvatum	Very frequent (present in 80%-99% of cases)
Intellectual disability	Very frequent (present in 80%-99% of cases)
Neurological speech impairment	Very frequent (present in 80%-99% of cases)
Peripheral neuropathy	Very frequent (present in 80%-99% of cases)
Seizures	Very frequent (present in 80%-99% of cases)
Amaurosis fugax	Frequent (present in 30%-79% of cases)
Hyperreflexia	Frequent (present in 30%-79% of cases)
Joint stiffness	Frequent (present in 30%-79% of cases)
Muscular hypotonia	Frequent (present in 30%-79% of cases)
Nystagmus	Frequent (present in 30%-79% of cases)
Optic atrophy	Frequent (present in 30%-79% of cases)
Spasticity	Frequent (present in 30%-79% of cases)
Aganglionic megacolon	Occasional (present in 5%-29% of cases)
Abnormality of the cerebral white matter	-
Autosomal recessive inheritance	-
Babinski sign	-
Bulbar palsy	-
Cholecystitis	-
Chorea	-
Delusions	-
Dysarthria	-
Dystonia	-
EMG: neuropathic changes	-
Emotional lability	-
Gallbladder dysfunction	-
Hallucinations	-
Hyporeflexia	-
Increased CSF protein	-
Loss of speech	-
Mental deterioration	-
Peripheral demyelination	-
Progressive peripheral neuropathy	-
Spastic tetraplegia	-
Tetraplegia	-
Urinary incontinence	-

Last updated: 9/1/2017

Inheritance Inheritance

Metachromatic leukodystrophy is inherited in an autosomal recessive manner. This means that both copies of the disease-causing gene in each cell must have a mutation for an individual to be affected. Individuals inherit two copies of each gene - one copy from each parent. Typically, an individual is affected because they inherited a mutated copy of the gene from each parent. Individuals with one mutated copy of the gene (such as an unaffected parent of an affected individual) are referred to as carriers; carriers typically do not have any signs or symptoms of the condition.

When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to have the condition, a 50% (1 in 2) chance to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Last updated: 6/28/2012

Diagnosis Diagnosis

If someone has a family history of metachromatic leukodystrophy (MLD) or someone is known to be a carrier for MLD, individuals who are biologically related to the affected individual or carrier are at risk to be a carrier. Generally speaking, the more closely related an individual is to the affected individual or carrier, the greater the chance for that person to be a carrier. Prior to genetic testing, the chance to be a carrier for some biological relatives of an affected individual are as follows:

Parent of affected individual: assumed to be 100% (called an obligate carrier)
Unaffected sibling of affected individual: 2 in 3 (~66.6%)
Aunt or uncle of affected individual: 1 in 2 (50%)
First cousin of affected individual: 1 in 4 (25%)

If someone has carrier testing and is found to be negative (not a carrier), that person's children are typically assumed to be negative also.

More information about the use of genetic carrier testing is available on GeneTests' Web site and can be viewed by clicking here.

Individuals who are interested in learning about genetic testing and about their specific risk to be a carrier should speak with a genetics professional.

Last updated: 6/28/2012

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

The prognosis for metachromatic leukodystrophy (MLD) is poor.^[2] The late infantile form of the disorder, the most common type, usually appears in the second year of life. This form typically progresses over approximately 5 to 10 years.^[3] Most children with the infantile form die by age 5.^[2] The juvenile form, with onset between the age of 4 and adolescence, has a slower progression than the late infantile form and symptoms may develop over 10 to 20 years; death typically occurs 10 to 20 years following onset.^[2]^[3] In the adult form, the first symptoms typically appear during the teenage years or later. This form may possibly progress over 20 to 30 years, although many individuals with the adult form die within 6 to 14 years following the onset of symptoms.^[2]^[3] During the progression of this form there may be some periods of relative stability and other periods of more rapid decline.^[3]

Last updated: 5/9/2012

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Metachromatic leukodystrophy. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

MLD Foundation
21345 Miles Drive
West Linn, OR 97068-2878
Toll-free: 800-617-8387
Telephone: 503-656-4808
Fax: 503-212-0159
E-mail: info@mldfoundation.org
Website: http://mldfoundation.org/
United Leukodystrophy Foundation (ULF)
224 North Second Street
Suite 2
DeKalb, IL 60115
Toll-free: 800-728-5483
Telephone: 815-748-3211
Fax: 815-748-0844
E-mail: office@ulf.org
Website: http://www.ulf.org/

Organizations Providing General Support

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Financial Resources

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The American Society of Gene & Cell Therapy provides information on the treatment of lysosomal storage diseases.
Genetics Home Reference (GHR) contains information on Metachromatic leukodystrophy. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Metachromatic leukodystrophy. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Gordon Research Conference and Gordon Research Seminar on Lysosomes and Endocytosis Sunday, June 15, 2014 - Friday, June 20, 2014
Location: Proctor Academy, Andover, NH
Description: The main goal of the Lysosomes and Endocytosis GRC is to foster the dissemination of current research results and the establishment of new research areas and new collaborations in the area of the cell biology of endocytosis, lysosomes, endosomes and related organelles. We hope that many of these new directions and collaborations will be directed toward the etiology, diagnosis and treatment of rare genetic diseases such as lysosomal storage disorders, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Niemann Pick disease and tuberous sclerosis, among others.

Contact: Alexandra Ainsztein, Ph.D.(301) 594-0828, Alexandra.Ainsztein@nih.gov

Co-funding Institute(s): National Institute of General Medical Sciences, Office of Rare Diseases Research
WORLD Symposium 2010 (Lysosomal Disease Network's 6th Annual Research Meeting) Wednesday, February 10, 2010 - Friday, February 12, 2010
Location: Miami Hilton Downtown, Miami, Florida
Description: The specific aims of this meeting were to (1) emphasize the strategies for, and identify the obstacles to, moving from translational research to clinical trials; (2) coalesce members of the LD network into functional research collaborations and present to the LDN community progress on the specific projects that are part of the funded U54 RDCRN grant; (3) foster interdisciplinary collaboration with the overall goal of improving knowledge of basic discoveries and clinical manifestations of these diseases; (4) provide an educational forum for young investigators, clinicians, and researchers in the field; (5) identify and discuss the latest findings in the natural history of lysosomal diseases, diagnostic testing and screening, and treatment, with specific focus on (a) inflammatory components of lysosomal diseases and autophagy, especially in the central nervous system, (b) new treatments of the central nervous systems, and (c) ethics and efficacy in treating the presymptomatic or asymptomatic patient; and (6) identify areas requiring additional basic and clinical research and public policy and regulatory attention, such as ethics and economics, and factors that impact implementation of therapy, including newborn screening.

Contact: Dr. Danilo A. Tagle(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 2715KB)

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GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My 2 year old grandson has MLD. So both parents are carriers. I have three other children and 2 of them have one child each. All 3 of my other children are planning to have another child. Who in the family needs to be tested for the carrier gene for MLD? Does a child of a carrier automatically become a carrier as well? Will that carrier gene continue to be passed on and should all my family be tested? See answer
We found out my cousin has metachromatic leukodystrophy about 8 months ago. He has the adult form. He was having some problems about a year before we found out. I was wondering how long he might have to live and how bad the disease will get over time. See answer

Have a question? Contact a GARD Information Specialist.