1994 Woodrow Wilson Biology Institute
The students will observe the scientific method being put into practice. This is a true-life drama which depicts the social, financial, ethical and political ramifications of a little-known genetic disease that doesn't get much attention from doctors nor the research community.
This is an interdisciplinary study that could be used on several levels and with a variety of classes, for example: Biology, Chemistry, Genetics, Ethics, Health, Neurology, Nutrition, Pathology, Psychology and Anatomy.
ALD is an X-linked recessive inheritance of a syndrome of Addison disease and cerebral sclerosis. It only affects males although neonatal autosomal ALD may also affect females. This neonatal form is clearly separate from the X-linked ALD. Symptoms often appear in boys between the ages of 4 and 8 and may include behavioral changes such as poor memory, loss of emotional control and dementia. Other symptoms may include muscle weakness, difficulties with hearing, speech and vision.
The symptoms of ALD may develop due to abnormal or absent peroxisomes (microbodies that participate in the metabolism of fats) in the liver. This causes a disturbance of fatty acid metabolism and results in the abnormal accumulation of very long chain fatty acids. The exact enzyme deficiency that prevents the breakdown of VLCFAs is not known.
ALD is an allelic mutation. This disease is caused by a single mutation at the locus Xq28. There is a close linkage of ALD to the cluster of color-blindness genes. This single mutation causes deficient activity of the necessary enzyme ligase. There is a 50% chance the disease will be passed from mother to offspring. The male will express the disease and the female will be a carrier.
Diagnosis can be made from cultured skin fibroblasts or amniotic fluid cells and allows prenatal diagnosis and carrier identification of 90% of obligate heterozygotes. More recently it has been shown that the biochemical diagnosis can be performed on chorionic villi biopsy.
This disease can be prevented with a combined approach of oleic acid (Lorenzo's Oil) and a restricted diet minus very long fatty acids. Also some ALD patients have been treated experimentally with Glycerol Trioleate. More research is needed to determine the long-term safety and effectiveness of these substances.
The prognosis is excellent for those individuals who are identified prenatally or shortly after birth. There can be normal functions for those individuals who take the prescribed dose of oil and follow the restricted diet regimen.
This film is based on a true story which took place from l984 to l987. The sobering news that their five year old son Lorenzo has a rare terminal disease marks the beginning of an extraordinary mission for Augusto and Michalla Odone. Despite the prognosis of death in two years because no treatment was known, the Odones set out to save their child, colliding with doctors, scientists, and support groups who are reluctant to encourage the couple in their quest for a cure. Their relentless struggle tests the strength of their marriage, the depth of their beliefs, and the boundaries of conventional medicine.
The film shows how individuals can make a difference and by using models and the scientific method the Odones discover by trial and error a treatment for ALD. The film ends on a positive note by showing several healthy children who are presently taking Lorenzo's Oil and are symptom-free of the disease. It is very heart-warming to see these normal children and know they have only the Odones to thank for their normal lives.
Another positive ending is the Myelin Project which has been funded by the national government to find a way to restore the myelin sheath which surrounds nerve cells. If the myelin can be restored, patients like Lorenzo can lead a normal life. The conclusion relates that Lorenzo can communicate by using a computer and his father, Augusto Odone, has been awarded an honorary Ph.D. for his pioneering work in researching and discovering a significant treatment for ALD.
Lewis Ricki, Human Genetics, Concepts and Applications, Wm. C. Brown Publishers, Oxford, England, l994.
"Lorenzo's Oil," MCA Universal Studio, l992.
McKusick, Victor A., M.D., Mendelian Inheritance in Man, 9th Ed., Johns Hopkins University Press, Baltimore, Maryland, l990. (Available online at NIH)
National Organization for Rare Disorders (NORD)
P.O. Box 8923
New Fairfield, CT 06812-1783
Dr. Hugo W. Moser
John F. Kennedy Institute
707 North Brockway
Baltimore, MD 21205
For Genetic Information and Genetic Counseling Referrals:
March of Dimes Birth Defects Foundation
1275 Mamaroneck Avenue
White Plains, NY 10605