Genetic disorders run the gamut from mild to severe. Research is being conducted on effective treatments for them around the globe. In addition, dedicated individuals are banding together to raise awareness of them and increase the level of screening. I interviewed two moms: Patti Chapman, who is president of the Myelin Project, located in Pacific Palisades, California, and Elisa Seeger, who was instrumental in the passage of Aidan’s Law in New York. Both women have personal experience with a rare but devastating disorder: adrenoleukodystrophy (ALD). The disease destroys the adrenal glands and causes severe deterioration of the central nervous system. The genetic mutation is on the X chromosome, meaning that the vast majority of affected individuals are males. Most women with the mutation only have one abnormal gene; thus, they are not affected, or in some cases, only minimally affected. However, they can transmit the defective gene to their sons.
Although many are not aware of ALD, some may remember the 1992 movie Lorenzo’s Oil. The film documents the Odone’s family to develop a treatment of ALD in their son. The boy’s father created Lorenzo’s oil, which is a combination of two chemicals called erucic acid and oleic acid. It is somewhat effective in treating ALD.
Patti Chapman knows firsthand the devastating effects of ALD. Her three brothers all inherited the gene. Her younger brother, Bobby was misdiagnosed, and treated for a brain tumor in the late-1950s. He died in 1960 just before his fifth birthday. In the mid-1980s, her youngest brother Richard began to develop symptoms of adrenomyeloneuropathy (AMN), which is the adult form of the disease. Richard was diagnosed in in 1987 and passed away in 2001. As a result of his diagnosis, Patti and her sisters were tested for the genetic defect. Patti is the only carrier of the disease in her immediate family. Patti’s three sons were subsequently tested; her eldest son, Michael, was the only one who inherited the genetic defect. He immediately started taking Lorenzo’s Oil, under the assumption that he would develop symptoms of ALD. Unfortunately, his disease progressed, Patti, informed me that he is now age 33 and “very symptomatic.” He will soon be confined to a wheelchair. Patti became the president of The Myelin Project in 2009 and part of their mission and funding is to advocate for newborn screening. The organization currently funds the newborn screening program at Kennedy Krieger Institute.
Elisa Seeger was instrumental in the passage of Aidan's Law on March 29, 2013 in New York. Their son, Aidan, died from ALD after spending his entire seventh year of life—10 months—in the hospital. Aidan’s symptoms first appeared when he was in the first grade. After a series of doctor visits, during which his symptoms worsened, the diagnosis was made. On his seventh birthday he received a successful bone-marrow transplant at Duke University Hospital in North Carolina; however, his physical and mental condition deteriorated. He lost his ability to see, eat and speak; he died on April 29. He would have fared much better, and perhaps be in relatively good health if he had been diagnosed with the disorder at birth and had received a transplant when the first symptoms appeared.
Elisa told me that during the year since the passage of Aidan’s Law, four infants have been diagnosed with ALD. The genetic test has been added to a panel of newborn genetic tests—the added cost, a mere $1.50. Patti has joined forces with Assemblyman Richard Pan, D-Sacramento, who is a pediatrician and author of AB 1559, which, if passed, will mandate ALD screening of newborns in California. They are pleading their case before a State Assembly committee on April 1. Patti told me that the test might cost a few dollars more in California because three labs conduct genetic screening in the state. In New York, all specimens are sent to a single lab. The lab may also perform the test for other smaller states near New York.
Both Patti and Elisa note that they make up just one component of a global organization focused on ALD and AMN. It is too late to prevent the devastation that occurred in their families; however, their efforts will reduce the impact on other children and their families in New York, California, and other states as well.
ALD is one of a group of genetic disorders called the leukodystrophies; these diseases cause damage to the myelin sheath, which is an insulating membrane that surrounds nerve cells in the brain. People with ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex. The loss of myelin and the progressive dysfunction of the adrenal gland are the primary characteristics of the disease. Almost all patients with ALD suffer from adrenal insufficiency, also known as Addison's disease, the neurological symptoms can begin either in childhood or in adulthood. The childhood cerebral form is the most severe, with onset between ages 4 and 10. The most common symptoms are usually behavioral changes such as abnormal withdrawal or aggression, poor memory, and poor school performance. Other symptoms include visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia.
The milder adult-onset form, AMN, typically begins between ages 21 and 35. Symptoms may include progressive stiffness, weakness or paralysis of the lower limbs, and ataxia (lack of coordination of muscle movements). AMN progresses more slowly than the classic childhood form; however, it can also result in deterioration of brain function. Almost half the women who are carriers of ALS will develop a milder form of AMN; however, almost never will develop symptoms seen in boys with ALD.
All patients with ALD must have their adrenal function tested periodically; treatment with adrenal hormones can be lifesaving. Symptomatic and supportive treatments for ALD include physical therapy, psychological support, and special education. Recent evidence suggests that Lorenzo's Oil administered to boys with ALD prior to symptom onset can prevent or delay the appearance of the childhood cerebral form It is currently unknown whether Lorenzo's Oil will have any beneficial effects in AMN. In addition, Lorenzo's Oil has no beneficial effect in symptomatic boys with ALD. Bone marrow transplantations can provide long-term benefit to boys who have early evidence of the childhood cerebral form of ALD; however, the procedure carries risk of mortality (death) and morbidity (side-effects); thus, it is not recommended for those whose symptoms are already severe or who have the adult-onset or neonatal forms.
In general, the prognosis for patients with childhood cerebral ALD is generally poor due to progressive neurological deterioration unless bone marrow transplantation is performed early. Death usually occurs within 1 to 10 years after the onset of symptoms. Adult-onset AMN will progress over decades.
The aim of research on genetic disorders is to determine ways to prevent, treat, and cure these disorders. Studies are currently underway to identify new biomarkers of disease progression and to determine which patients will develop the childhood cerebral form of ALD. A recent case study in Europe reported that the combination of gene therapy with bone marrow transplantation, using the patient's own bone marrow cells, may arrest disease progression in childhood cerebral ALD. A therapeutic trial in the United States for this treatment is currently underway.
- P.O. Box 39
- Pacific Palisades, CA 90272
- Tel: 800-869-3546 310-459-1071
- Fax: 310-230-4298
National Organization for Rare Disorders (NORD)
- 55 Kenosia Avenue
- Danbury, CT 06810
- Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
- Fax: 203-798-2291
National Tay-Sachs and Allied Diseases Association
- 2001 Beacon Street
- Suite 204
- Boston, MA 02135
- Tel: 800-90-NTSAD (906-8723)
- Fax: 617-277-0134
United Leukodystrophy Foundation