Metachromatic leukodystrophy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords: Arylsulfatase A deficiency
Overview
Metachromatic leukodystrophy is the most common form of a family of genetic diseases known as the leukodystrophies, diseases which affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibres throughout the central and peripherial nervous systems .
Historical Perspective
Classification
Pathophysiology
Gene Therapy
- two trials are in the planning stages in Europe, one in Italy and one in France
Clinical trial updates provided by the MLD Foundation
Causes
MLD is directly caused by a deficiency of the enzyme arylsulfatase A. Without this enzyme, sulfatides build up in many tissues of the body, eventually destroying the myelin of the nervous system.
Differentiating Metachromatic leukodystrophy from Other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Like many other genetic disorders that affect lipid metabolism, there are several forms of MLD, which are late infantile, juvenile, and adult.
In the late infantile form, which is the most common form MLD, affected children begin having difficulty walking after the first year of life. Symptoms include muscle wasting and weakness, muscle rigidity, developmental delays, progressive loss of vision leading to blindness, convulsions, impaired swallowing, paralysis, and dementia. Children may become comatose. Untreated, most children with this form of MLD die by age 5, often much sooner.
Children with the juvenile form of MLD (onset between 3-10 years of age) usually begin with impaired school performance, mental deterioration, and dementia and then develop symptoms similar to the late infantile form but with slower progression. Age of death is variable, but normally within 10 to 15 years of symptom onset.
The adult form commonly begins after age 16 as a psychiatric disorder or progressive dementia. Adult-onset MLD progresses more slowly than the late infantile and juvenile forms, with a protracted course of a decade or more.
In rare cases the body can compensate for the deficiency and the person will exhibit no symptoms.
Physical Examination
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
There is no cure for MLD, nor a standard form of treatment. Children with advanced juvenile or adult onset, and late infantile patients displaying symptoms have treatment limited to pain and symptom management. Presymptomatic late infantile MLD patients, as well as those with juvenile or adult MLD that are either presymptomatic or displaying mild to moderate symptoms, have the option of bone marrow transplantation (including stem cell transplantation), which may slow down the progression of the disease, or stop its progression in the central nervous system, however results in the peripheral nervous system have been less dramatic.
Treatment options for the future that are currently being investigated include gene therapy and enzyme replacement therapy (ERT), and potentially a enzyme enhancement therapy (EET).
Medical Therapy
Surgery
Prevention
Future or Investigational Therapies
Clinical Trials
Enzyme Replacement Therapy
- Phase II clinical trials are underway in Europe by a Danish company, Zymenex, using Metazym, (updated August 2007)
- Shire Human Genetics is proposing an enzyme replacement therapy
See also
External links
- Large portions of this article are courtesy of the public domain text available at the National Institute of Neurological Disorders and Stroke [2]
- Further information regarding MLD, treatments, genetics, and current research projects, can be found at:
- eMedicine article about MLD by Theodore Moore, MD.
- mld at NIH/UW GeneTests
References
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