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Disease Profile

Metachromatic leukodystrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Childhood

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ICD-10

E75.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Leukodystrophy metachromatic; Metachromatic leukoencephalopathy; MLD;

Categories

Metabolic disorders

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]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal enzyme/coenzyme activity
0012379
Periventricular leukomalacia
0006970
30%-79% of people have these symptoms
Abnormality of visual evoked potentials
0000649
Ataxia
0001251
Decreased nerve conduction velocity
0000762
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
Frequent falls
0002359
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hyperintensity of cerebral white matter on MRI
0030890
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Increased CSF protein
0002922
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Muscle spasm
0003394
Muscle weakness
Muscular weakness
0001324
Peripheral neuropathy
0009830
Progressive spasticity
0002191
Seizure
0001250
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
5%-29% of people have these symptoms
Addictive behavior
0030858
Bowel incontinence
Loss of bowel control
0002607
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Dysarthria
Difficulty articulating speech
0001260
Dystonia
0001332
Emotional lability
Emotional instability
0000712
Gastrostomy tube feeding in infancy
0011471
Limb pain
0009763
Personality changes
Personality change
0000751
Psychosis
0000709
Schizophrenia
0100753
Toe walking
Toe-walking
0040083
Tremor
0001337
Urinary incontinence
Loss of bladder control
0000020
1%-4% of people have these symptoms
Abnormal duodenum morphology
0002246
Abnormal stomach morphology
0002577
Decerebrate rigidity
0025013
Hemobilia
0100762
Intussusception
0002576
Neoplasm of the gallbladder
0100575
Percent of people who have these symptoms is not available through HPO
Abnormality of the cerebral white matter
0002500
Autosomal recessive inheritance
0000007
Babinski sign
0003487
Bulbar palsy
0001283
Cholecystitis
Gallbladder inflammation
0001082
Chorea
0002072
Delusions
0000746
EMG: neuropathic changes
0003445
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Gallbladder dysfunction
0005609
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hallucinations
Hallucination
Sensory hallucination

[ more ]

0000738
Hyperreflexia
Increased reflexes
0001347
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Loss of speech
0002371
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Muscular hypotonia
Low or weak muscle tone
0001252
Optic atrophy
0000648
Peripheral demyelination
0011096
Progressive peripheral neuropathy
0007133
Spastic tetraplegia
0002510
Tetraplegia
Paralysis of all four limbs
0002445

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.

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.

    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

      Organizations Providing General Support

        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

          In-Depth Information

          • 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.
          • 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.

            References

            1. Metachromatic leukodystrophy. Genetics Home Reference. February 2013; https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy. Accessed 9/19/2014.
            2. Metachromatic Leukodystrophy Information Page. National Institute of Neurological Disorders and Stroke (NINDS). June 22, 2018; https://www.ninds.nih.gov/Disorders/All-Disorders/Metachromatic-Leukodystrophy-Information-Page.
            3. Metachromatic leukodystrophy. Genetics Home Reference. September 2007; https://ghr.nlm.nih.gov/condition/metachromatic-leukodystrophy. Accessed 5/9/2012.

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