Friedreich's Ataxia Health Article

Definition

Friedreich's ataxia (FA) is an inherited, progressive nervous system disorder causing loss of balance and coordination, speech problems, and heart disease.

Description

FA is an inherited disease marked by impaired coordination that is a result of degeneration of the structures in the cerebellum and the spinal cord, which are responsible for coordination, muscle movement, and some sensory functions, including color vision and hearing. The intellect of a child with FA is normal.

FA is an autosomal recessive disease, which means that two defective gene copies, one from each parent, must be inherited to develop symptoms. A person with only one defective gene copy will not show signs of FA, but may pass along the gene to offspring. Couples with one child affected by FA have a 25 percent chance in each pregnancy of conceiving another affected child.

FA is also referred to as spinocerebellar degeneration.

Demographics

Friedreich's ataxia is the most common inherited ataxia, affecting one in 50,000 people in the United States. Females and males are affected equally.

Causes

The gene for FA codes for a protein called frataxin. Normal frataxin is found in the cellular energy structures known as mitochondria, where it is thought to be involved in regulating the transport of iron. In FA, the frataxin gene on chromosome 9 is expanded when a particular sequence of bases in the DNA is repeated too many times. Ordinarily, there are seven to 22 repeats of the frataxin gene; in FA, this sequence may be repeated between 800 to 1,000 times. This extra DNA interferes with normal production of frataxin, thereby impairing iron transport. The triplet repeat expansion seems to interfere with the normal assembly of amino acids into proteins, significantly reducing the amount of frataxin that is made. Without a normal level of frataxin, some of the body's cells—especially those of the brain, spinal cord, and muscle—cannot handle the normal amounts of "oxidative stress," which the mitochondria produce. When excess iron in the cells (as a result of the deficiency of frataxin) reacts with oxygen, free radicals are produced. Free radicals are necessary molecules in the body's metabolism, but in excess they can also destroy cells and harm the body.

The types of symptoms and severity of FA seems to be associated with the number of repetitions. Children with more copies have more severe symptomatology, with symptoms starting at a younger age.

The nerve cells most affected by FA are those in the spinal cord involved in relaying information between muscles and the brain. Control of movement requires complex feedback between the muscles promoting a movement, those restraining it, and the brain. Without this control, movements become uncoordinated, jerky, and inappropriate to the desired action.

Symptoms

Symptoms of FA usually first appear between the ages of five and 15 years, although onset as early as 18 months or as late as age 30 years is possible. The first symptom is usually gait incoordination. A child with FA may graze doorways when passing through, for instance, or trip over low obstacles. Unsteadiness when standing still and deterioration of position sense is common. Children with FA may develop foot deformities such as club-foot, hammertoe, and high arches. Walking up off the heels often results from uneven muscle weakness in the legs. Muscle spasms and cramps may occur, especially at night. Other early symptoms include changes in speech, swallowing difficulties, loss of reflexes, and jerky eye movements (nystagmus).

Ataxia in the arms follows, usually within several years, leading to decreased hand-eye coordination. Arm weakness does not usually occur until much later. There is often a gradual loss of sensation in the extremities, which may spread to other parts of the body. In about 10 percent of children with FA, diabetes mellitus may develop in the later stages of the disease. Some loss of visual acuity may be noted. Hearing loss occurs in about 10 percent of children with FA, and about 20 percent develop carbohydrate intolerance. A side-to-side curvature of the spine (scoliosis) occurs in many cases, and may become severe. About 50 percent of people develop problems with control of their urge to urinate (urinary urgency), or become incontinent.

Various forms of heart disease often accompany FA, including cardiomyopathy (enlargement of the heart), myocardial fibrosis (formation of fiber-like materials in heart muscles), and cardiac failure. Symptoms of heart involvement include chest pain, shortness of breath, and heart palpitations. Heartbeat abnormalities such as tachycardia (rapid heart rate) and heart block (impaired conduction of the heart's cardiac impulses) are common occurrences.

When to call the doctor

Any time a child with FA reports unusual heart symptoms, such as shortness of breath on exertion, dizziness, fainting, chest pain or discomfort, or abnormal heart rhythms, the doctor or cardiologist should be called, or the child should be taken immediately to a hospital emergency room.