A Difficult Decision: Huntington’s Disease
I have said that the color of medicine is gray. This is true in many areas of medicine. One of the more difficult areas that must be faced is in Huntington's disease (HD). Following a brief summary of the disease itself, we will examine the exceedingly difficult decisions that must be made when faced with HD. The name, Huntington's disease is derived from Huntington's chorea, which gets its name from the American physician who wrote about it in 1872; although, more than likely, the disease was described in the middle ages.
In the United States, about 30,000 people suffer from HD. The estimated prevalence is about 1 in 10,000 persons, which is similar to that for PKU. More than 150,000 others have at least a 50:50 chance of developing the disease for which there is no cure. Additional thousands may also develop the disease.
HD is quite variable in its age of onset-the adult form most often shows its signs in middle age with the uncontrolled movements. Some HD termed juvenile onset begins before age 20, often by age 10. In these cases, the symptoms may show as subtle changes in handwriting or muscle twitching. A few persons develop HD after age 55. In these patients the diagnosis is often more difficult.
HD is a genetic disease resulting in degeneration of neurons in certain areas of the brain. The gene for HD has been located on chromosome 4, one of the non-sexed linked genes. HD, an autonomic dominant disorder, requires only one copy of the gene to be present to cause the disease. The mutation of the gene results in several base pairs-C, A and G-being repeated several dozen times. A child of a parent with HD has a 50:50 chance of inheriting HD. A child who inherits the gene and survives long enough will develop the HD, perhaps after having passed the gene onto one or more of his or her children. This is because most cases do not appear until the person has reached puberty and can conceive a child. It is this aspect of the disease, differing from PKU, which can be diagnosed in the first few weeks of life that leads to the difficult decisions.
Woodie Guthrie, a folk singer and composer, died in 1967 after suffering from HD for 13 years. His son, Arlo, also a singer, is now 60 and has shown no signs of HD. Woody had been misdiagnosed, considered an alcoholic and was in and out of mental hospitals for a number of years. His case is not exceptional-HD is often missed. It can usually be diagnosed correctly by an experienced neurologist. Today, thanks to the discovery in 1993 of the gene for HD, there is a laboratory test of the person's DNA. In this test the number of CAG base pairs (this triplet codes for glutamine) repeats in the region of the gene can be counted will be helpful in assessing the patient's risk for HD. The gene where these repeats occur has been given the name huntingtin. The function of this protein is currently not known.
- Patients with no more than 28 repeats will not develop HD.
- Patients with 29 - 34 will not develop HD, but the next generation is at risk as the mutant gene appears to increase the number of repeats with each generation.
- In those with 35 - 39 repeat some, but not all, persons will develop HD, and the next generation will be at increased risk.
- Those patients with 40 or more repeats of CAG will develop HD.
In some cases a CT or MRI will be requested. These, though, are not specific for HD.
There is no treatment to stop or even slow the progression of this debilitating and fatal disease. Some antipsychotic and antidepressant drugs may reduce the symptoms of HD. Over the past 20 years and quite recently cysteamine has been used as a treatment for the motor symptoms. This has met with limited success.
The decisions. Consider a person recently diagnosed with HD who also has children. These children carry a 50 percent chance of developing HD as well as transmitting the gene to their children. The decision the children have is whether to be tested to know if in the future (perhaps many years in the future) they will (or will not) develop HD. In addition, that test will indicate something about the risk of their children developing HD. If the children of the patient are tested and found to carry the gene, they must decide whether to have children of their own. Today with in vitro fertilization it is possible to screen the embryos for HD and use only those that are do not carry the mutant gene. This scenario leads to another set of difficult practical, financial and ethical questions.
The children of the patient must decide whether to tell their spouse or spouse to be that they are a carrier of HD.
Consider the physician who may be asked to make the diagnosis. May a physician choose not to assist in such a diagnosis? Or at least not without a thorough discussion of the genetics of HD and the possible outcomes of the test, and the paths to take once the diagnosis is at hand? Is the physician obligated to tell the patient that a test exists for the children of the patient?
It is possible that sometimes our technology outruns our ability to deal with the answers and the new questions such technology forces us to consider.