Huntington's Disease Causes, Symptoms, Diagnosis, Treatment,Prevention

Huntington's Disease Causes, Symptoms, Diagnosis, Treatment,Prevention

About Huntington's Disease

Huntington's disease is a progressive brain disorder caused by a single defective gene on chromosome 4 — one of the 23 human chromosomes that carry a person’s entire genetic code. 

This defect is "dominant," meaning that anyone who inherits it from a parent with Huntington's will eventually develop the disease. The disorder is named for George Huntington, the physician who first described it in the late 1800s.

The defective gene codes the blueprint for a protein called huntingtin. This protein's normal function isn't yet known, but it's called "huntingtin" because scientists identified its defective form as the cause of Huntington's disease. Defective huntingtin protein leads to brain changes that cause abnormal involuntary movements, a severe decline in thinking and reasoning skills, and irritability, depression and other mood changes.

What causes Huntington's disease?

Huntington's Disease results from genetically programmed degeneration of nerve cells, called neurons,* in certain areas of the brain. This degeneration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance. Specifically affected are cells of the basal ganglia, structures deep within the brain that have many important functions, including coordinating movement. Within the basal ganglia, Huntington's Disease especially targets neurons of the striatum, particularly those in the caudate nuclei and the pallidum. Also affected is the brain's outer surface, or cortex, which controls thought, perception, and memory.

What are the symptoms and  major effects of Huntington's disease?

Early signs of the disease vary greatly from person to person. A common observation is that the earlier the symptoms appear, the faster the disease progresses.

Family members may first notice that the individual experiences mood swings or becomes uncharacteristically irritable, apathetic, passive, depressed, or angry. These symptoms may lessen as the disease progresses or, in some individuals, may continue and include hostile outbursts or deep bouts of depression.

Huntington's Disease may affect the individual's judgment, memory, and other cognitive functions. Early signs might include having trouble driving, learning new things, remembering a fact, answering a question, or making a decision. Some may even display changes in handwriting. As the disease progresses, concentration on intellectual tasks becomes increasingly difficult.

In some individuals, the disease may begin with uncontrolled movements in the fingers, feet, face, or trunk. These movements--which are signs of chorea--often intensify when the person is anxious. Huntington's Disease can also begin with mild clumsiness or problems with balance. Some people develop choreic movements later, after the disease has progressed. They may stumble or appear uncoordinated. Chorea often creates serious problems with walking, increasing the likelihood of falls.

The disease can reach the point where speech is slurred and vital functions, such as swallowing, eating, speaking, and especially walking, continue to decline. Some individuals cannot recognize other family members. Many, however, remain aware of their environment and are able to express emotions.

Some physicians have employed a recently developed Unified HD Rating Scale, or UHDRS, to assess the clinical features, stages, and course of Huntington's Disease. In general, the duration of the illness ranges from 10 to 30 years. The most common causes of death are infection (most often pneumonia), injuries related to a fall, or other complications.

How do doctors diagnose Huntington's Disease?

During pregnancy a woman can find out if her baby will have the disease with two tests: taking a sample of fluid from around the fetus (amniocentesis), or by taking a sample of fetal cells from the placenta (chorionic villus sampling (CVS)).

After the child is born, doctors can identify the disease by first doing a series of neurological and psychological tests. A genetic test can then confirm the diagnosis by determining if the person indeed has inherited the Huntington's Disease gene mutation (an expansion of the CAG triplet). However, the test cannot tell at what age a person will begin to get sick.

Treatment for Huntington's disease?

Physicians may prescribe a number of medications to help control emotional and movement problems associated with Huntington's Disease. It is important to remember however, that while medicines may help keep these clinical symptoms under control, there is no treatment to stop or reverse the course of the disease.

In August 2008 the U.S. Food and Drug Administration approved tetrabenazine to treat Huntington's chorea, making it the first drug approved for use in the United States to treat the disease. Antipsychotic drugs, such as haloperidol, or other drugs, such as clonazepam, may help to alleviate choreic movements and may also be used to help control hallucinations, delusions, and violent outbursts. Antipsychotic drugs, however, are not prescribed for another form of muscle contraction associated with Huntington's Disease, called dystonia, and may in fact worsen the condition, causing stiffness and rigidity. These medications may also have severe side effects, including sedation, and for that reason should be used in the lowest possible doses.

For depression, physicians may prescribe fluoxetine, sertraline, nortriptyline, or other compounds. Tranquilizers can help control anxiety and lithium may be prescribed to combat pathological excitement and severe mood swings. Medications may also be needed to treat the severe obsessive-compulsive rituals of some individuals with Huntington's Disease.

Most drugs used to treat the symptoms of Huntington's Disease have side effects such as fatigue, restlessness, or hyperexcitability. Sometimes it may be difficult to tell if a particular symptom, such as apathy or incontinence, is a sign of the disease or a reaction to medication.

How to Prevent Huntington's Disease

There is no way to prevent the onset of Huntington's Disease if a person has inherited the gene for the disorder. Medicines aimed at slowing and treating the disease progression are being studied. A prospective parent with Huntington's Disease or a family history of Huntington's Disease can seek genetic counseling when deciding whether or not to have children. Genetic counseling is extremely important since half of the children of an affected parent are at risk for inheriting Huntington's Disease.

How is Huntington's disease inherited?

Huntington's Disease is found in every country of the world. It is a familial disease, passed from parent to child through a mutation or misspelling in the normal gene.

A single abnormal gene, the basic biological unit of heredity, produces Huntington's Disease. Genes are composed of deoxyribonucleic acid (DNA), a molecule shaped like a spiral ladder. Each rung of this ladder is composed of two paired chemicals called bases. There are four types of bases--adenine, thymine, cytosine, and guanine--each abbreviated by the first letter of its name: A, T, C, and G. Certain bases always "pair" together, and different combinations of base pairs join to form coded messages. A gene is a long string of this DNA in various combinations of A, T, C, and G. These unique combinations determine the gene's function, much like letters join together to form words. Each person has about 30,000 genes--a billion base pairs of DNA or bits of information repeated in the nuclei of human cells--which determine individual characteristics or traits.

Genes are arranged in precise locations along 23 rod-like pairs of chromosomes. One chromosome from each pair comes from an individual's mother, the other from the father. Each half of a chromosome pair is similar to the other, except for one pair, which determines the sex of the individual. This pair has two X chromosomes in females and one X and one Y chromosome in males. The gene that produces Huntington's Disease lies on chromosome 4, one of the 22 non-sex-linked, or "autosomal," pairs of chromosomes, placing men and women at equal risk of acquiring the disease.

The impact of a gene depends partly on whether it is dominant or recessive. If a gene is dominant, then only one of the paired chromosomes is required to produce its called-for effect. If the gene is recessive, both parents must provide chromosomal copies for the trait to be present. Huntington's Disease is called an autosomal dominant disorder because only one copy of the defective gene, inherited from one parent, is necessary to produce the disease.

The genetic defect responsible for Huntington's Disease is a small sequence of DNA on chromosome 4 in which several base pairs are repeated many, many times. The normal gene has three DNA bases, composed of the sequence CAG. In people with Huntington's Disease, the sequence abnormally repeats itself dozens of times. Over time--and with each successive generation--the number of CAG repeats may expand further.

Each parent has two copies of every chromosome but gives only one copy to each child. Each child of an Huntington's Disease parent has a 50-50 chance of inheriting the Huntington's Disease gene. If a child does not inherit the Huntington's Disease gene, he or she will not develop the disease and cannot pass it to subsequent generations. A person who inherits the Huntington's Disease gene, and survives long enough, will sooner or later develop the disease. In some families, all the children may inherit the Huntington's Disease gene; in others, none do. Whether one child inherits the gene has no bearing on whether others will or will not share the same fate.

A small number of cases of Huntington's Disease are sporadic, that is, they occur even though there is no family history of the disorder. These cases are thought to be caused by a new genetic mutation-an alteration in the gene that occurs during sperm development and that brings the number of CAG repeats into the range that causes disease.

At what age does Huntington's disease appear?

The rate of disease progression and the age at onset vary from person to person. Adult-onset Huntington's Disease, with its disabling, uncontrolled movements, most often begins in middle age. There are, however, other variations of Huntington's Disease distinguished not just by age at onset but by a distinct array of symptoms. For example, some persons develop the disease as adults, but without chorea. They may appear rigid and move very little, or not at all, a condition called akinesia.

Some individuals develop symptoms of Huntington's Disease when they are very young--before age 20. The terms "early-onset" or "juvenile" Huntington's Disease are often used to describe Huntington's Disease that appears in a young person. A common sign of Huntington's Disease in a younger individual is a rapid decline in school performance. Symptoms can also include subtle changes in handwriting and slight problems with movement, such as slowness, rigidity, tremor, and rapid muscular twitching, called myoclonus. Several of these symptoms are similar to those seen in Parkinson's disease, and they differ from the chorea seen in individuals who develop the disease as adults. These young individuals are said to have "akinetic-rigid" Huntington's Disease or the Westphal variant of Huntington's Disease. People with juvenile Huntington's Disease may also have seizures and mental disabilities. The earlier the onset, the faster the disease seems to progress. The disease progresses most rapidly in individuals with juvenile or early-onset Huntington's Disease, and death often follows within 10 years.

Individuals with juvenile Huntington's Disease usually inherit the disease from their fathers. These individuals also tend to have the largest number of CAG repeats. The reason for this may be found in the process of sperm production. Unlike eggs, sperm are produced in the millions. Because DNA is copied millions of times during this process, there is an increased possibility for genetic mistakes to occur. To verify the link between the number of CAG repeats in the Huntington's Disease gene and the age at onset of symptoms, scientists studied a boy who developed Huntington's Disease symptoms at the age of two, one of the youngest and most severe cases ever recorded. They found that he had the largest number of CAG repeats of anyone studied so far--nearly 100. The boy's case was central to the identification of the Huntington's Disease gene and at the same time helped confirm that juveniles with Huntington's Disease have the longest segments of CAG repeats, the only proven correlation between repeat length and age at onset.

A few individuals develop Huntington's Disease after age 55. Diagnosis in these people can be very difficult. The symptoms of Huntington's Disease may be masked by other health problems, or the person may not display the severity of symptoms seen in individuals with Huntington's Disease of earlier onset. These individuals may also show symptoms of depression rather than anger or irritability, or they may retain sharp control over their intellectual functions, such as memory, reasoning, and problem-solving.

There is also a related disorder called senile chorea. Some elderly individuals display the symptoms of Huntington's Disease, especially choreic movements, but do not become demented, have a normal gene, and lack a family history of the disorder. Some scientists believe that a different gene mutation may account for this small number of cases, bu this has not been proven.

What research is being done?

Scientific investigations using electronic and other technologies enable scientists to see what the defective gene does to various structures in the brain and how it affects the body's chemistry and metabolism. Laboratory animals are being bred in the hope of duplicating the clinical features of Huntington's Disease so that researchers can learn more about the symptoms and progression of Huntington's Disease. Investigators are implanting fetal tissue in rodents and nonhuman primates with the hope of understanding, restoring, or replacing functions typically lost by neuronal degeneration in individuals with Huntington's Disease. Related areas of investigation include excitotoxicity (overstimulation of cells by natural chemicals found in the brain), defective energy metabolism (a defect in the mitochondria), oxidative stress (normal metabolic activity in the brain that produces toxic compounds called free radicals), tropic factors (natural chemical substances found in the human body that may protect against cell death).