What is leukodystrophy? |

Causes and Symptoms

Leukodystrophy is caused by a breakdown in the enzyme systems that metabolize fats (lipids) in the nerve cells. As a result, the body can no longer break down very long chain fatty acids (VLCFA), which then accumulate. This causes the substance around nerve fibers, known as the myelin sheath, to degenerate. The myelin sheath protects and insulates the axons of nerve cells, allowing them to transmit impulses between the nerve cells in the brain and other parts of the body. Loss of the myelin sheath around nerve cells short-circuits nerve impulses. As a result, the victim can experience uncontrolled muscle stiffness, paralysis, speech difficulties, memory failures, personality changes, impaired reasoning, urinary incontinence, loss of vision, and loss of hearing. These symptoms may be difficult to recognize during the early stages of the disease. Leukodystrophy usually begins in the back of the brain, eventually spreading throughout the white matter of the cerebral hemispheres and often into
the spinal cord. Leukodystrophy is typically diagnosed with a blood test that is used to determine the amount of VLCFA in the body.

The myelin sheath is a complex chemical substance made from a variety of lipids. Different types of leukodystrophy affect one of the particular constituents of myelin. Specific leukodystrophies include adrenoleukodystrophy
(ALD), metachromatic leukodystrophy (MLD), Zellweger syndrome, and Alexander disease. Having one type of leukodystrophy does not increase the risk of having another type.

Treatment and Therapy

The effects of leukodystrophy may be tempered through the use of various medications, dietary supplements, exercise programs, and occupational and speech therapies. For ALD, the most common form of leukodystrophy, Lorenzo’s oil helps the body bring VLCFA levels back to normal. To be effective, Lorenzo’s oil should be coupled with a very-low-fat diet. Lovastatin, an anticholesterol drug, does the same thing as Lorenzo’s oil without the patient needing to be on a low-fat diet.

For some types of leukodystrophy, particularly MLD, bone marrow transplants have shown promise in slowing down the disease. Gene therapy is being investigated. The hope is to deliver genes to the patient that will stimulate the oligodendrocyte cells in the brain to produce myelin once again.

Perspective and Prospects

Leukodystrophy is genetically inherited. Most types show up in early childhood, although there are some late childhood forms. Public awareness of the disease was greatly enhanced by the 1992 film Lorenzo’s Oil, the true story of Augusto and Michaela Odone seeking a cure for ALD for their five-year-old son Lorenzo. They founded the Myelin Project, a research effort that continues to seek ways for victims of leukodystrophy to produce myelin that will insulate their nerve cells.

Bibliography

Canadian Agency for Drugs and Technologies in Health. Newborn Screening for Krabbe Leukodystrophy: A Review of the Clinical and Cost Effectiveness and Guidelines. Ottawa, Ont.: Author, 2012.

Icon Health. Leukodystrophy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004.

Kimball, Chad T. Childhood Diseases and Disorders Sourcebook: Basic Consumer Health Information About Medical Problems Often Encountered in Pre-adolescent Children. Detroit, Mich.: Omnigraphics, 2003.

Lazzarini, Robert A. Myelin Biology and Disorders. San Diego, Calif.: Academic Press/Elsevier, 2004.

Raymond Gerald V., et al. Leukodystrophies. London: Mac Keith Press for the International Child Neurology Association, 2011.

Salvati, S., ed. A Multidisciplinary Approach to Myelin Diseases II. New York: Plenum Press, 1994.