Metachromatic leukodystrophy

WikiDoc Resources for Metachromatic leukodystrophy
Articles
Most recent articles on Metachromatic leukodystrophy Most cited articles on Metachromatic leukodystrophy Review articles on Metachromatic leukodystrophy Articles on Metachromatic leukodystrophy in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Metachromatic leukodystrophy Images of Metachromatic leukodystrophy Photos of Metachromatic leukodystrophy Podcasts & MP3s on Metachromatic leukodystrophy Videos on Metachromatic leukodystrophy
Evidence Based Medicine
Cochrane Collaboration on Metachromatic leukodystrophy Bandolier on Metachromatic leukodystrophy TRIP on Metachromatic leukodystrophy
Clinical Trials
Ongoing Trials on Metachromatic leukodystrophy at Clinical Trials.gov Trial results on Metachromatic leukodystrophy Clinical Trials on Metachromatic leukodystrophy at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Metachromatic leukodystrophy NICE Guidance on Metachromatic leukodystrophy NHS PRODIGY Guidance FDA on Metachromatic leukodystrophy CDC on Metachromatic leukodystrophy
Books
Books on Metachromatic leukodystrophy
News
Metachromatic leukodystrophy in the news Be alerted to news on Metachromatic leukodystrophy News trends on Metachromatic leukodystrophy
Commentary
Blogs on Metachromatic leukodystrophy
Definitions
Definitions of Metachromatic leukodystrophy
Patient Resources / Community
Patient resources on Metachromatic leukodystrophy Discussion groups on Metachromatic leukodystrophy Patient Handouts on Metachromatic leukodystrophy Directions to Hospitals Treating Metachromatic leukodystrophy Risk calculators and risk factors for Metachromatic leukodystrophy
Healthcare Provider Resources
Symptoms of Metachromatic leukodystrophy Causes & Risk Factors for Metachromatic leukodystrophy Diagnostic studies for Metachromatic leukodystrophy Treatment of Metachromatic leukodystrophy
Continuing Medical Education (CME)
CME Programs on Metachromatic leukodystrophy
International
Metachromatic leukodystrophy en Espanol Metachromatic leukodystrophy en Francais
Business
Metachromatic leukodystrophy in the Marketplace Patents on Metachromatic leukodystrophy
Experimental / Informatics
List of terms related to Metachromatic leukodystrophy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chiranjeevi Sainatham, M.B.B.S[2]

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 .

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.

Diagnosis

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.

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).

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

• The Evanosky Foundation
• The MLD Foundation
• The Myelin Project
• The Stennis Foundation

External links

• Large portions of this article are courtesy of the public domain text available at the National Institute of Neurological Disorders and Stroke [3]
• Further information regarding MLD, treatments, genetics, and current research projects, can be found at:
  • The MLD Foundation
  • The Stennis Foundation
  • The Evanosky Foundation

• eMedicine article about MLD by Theodore Moore, MD.
• mld at NIH/UW GeneTests

References

Template:WikiDoc Sources