Azorean disease Health Article

Definition

Azorean disease causes progressive degeneration of the central nervous system. Affected individuals experience deterioration in muscle coordination and other physical symptoms, but intelligence and mental function remain unaffected by the disease.

Description

Azorean disease is an inherited disorder that causes impaired brain functioning, vision problems, and loss of muscle control. It is named for the Azores, the group of nine Portuguese islands where the disease is prevalent. Many of the reported cases have been found in the direct descendants of William Machado, an Azorean native who immigrated to the New England area of the United States, and Atone Joseph, a Portuguese sailor from the island of Flores who came to California in 1845. Other names for Azorean disease include Machado-Joseph disease, Joseph disease, and spinocerebellar ataxia type III.

Azorean disease is classified into three types depending on the age of onset and the specific physical symptoms. In type I, the age of onset is usually before age 25 and the affected individuals experience extreme muscle stiffness and rigidity. In type II, the age of onset is typically in the mid-30s, and progressive loss of muscle coordination (ataxia) occurs, resulting in the inability to walk. In type III, the average age of onset is 40 or later, and the main symptoms are weakness and loss of sensation in the legs.

The symptoms of Azorean disease result from the loss of brain cells and the impairment of neurological connections in the brain and spinal cord. This degradation of the central nervous system is believed to be caused by the production of a destructive protein from a mutated gene.

Genetic profile

Azorean disease is inherited as an autosomal dominant trait. This means that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome.

Each gene in the human body is made up of units called nucleotides, abbreviated C (cytosine), A (adenine), T (thymine), and G (guanine). A sequence of three nucleotides is called a trinucleotide. Azorean syndrome is caused by a genetic mutation that results in the over-duplication of a CAG trinucleotide sequence. The location of the mutant gene in Azorean disease is 14q32, on the long arm of chromosome 14. This gene normally encodes the formation of a cellular protein called ataxin- 3. In the general population, there are between 13 and 36 repeats of the CAG sequence, but in those individuals with Azorean disease, there may be between 61 and 84 repeats. The increased number of repetitions causes the gene to encode an abnormal protein product that is believed to cause cell death in the brain and spinal cord.

In successive generations, the number of the repetitions may increase, a phenomenon known as genetic anticipation. In addition, there appears to be a strong relationship between the number of repetitions and the age at onset of Azorean disease: the more repetitions, the sooner the disease presents and the more serious the symptoms are. Also, if the individual is homozygous for the mutated gene, meaning he or she inherits the gene from both parents, Azorean disease is more severe and the age of onset is as early as 16 years.

Demographics

Azorean disease is primarily found in people of Portuguese ancestry, particularly people from the Azores islands. In the Azores islands the incidence of Azorean disease is approximately one in every 4,000, while among those of Azorean descent, it is one in every 6,000. Azorean disease has also been identified in other ethnic groups, including Japanese, Brazilians, Chinese, Indians, Israelis, and Australian aborigines.

Signs and symptoms

The age of onset of Azorean disease is typically from the late teens to the 50s, although onset as late as the 70s has been reported. The first observable symptoms are difficulty in walking and slurred speech. There is wide variation in the range of observed symptoms, but they typically include problems with muscular coordination, eyes and vision, and other physical bodily functions such as speech and urination. Mental ability is not impaired by Azorean disease.

Muscular symptoms

Muscular symptoms observed in people with Azorean disease include:

• • difficulty in walking, including staggering or stumbling,
• • weakness in arms or legs,
• • involuntary jerking or spastic motions,
• • cramping or twisting of the hands and feet,
• • facial tics and grimaces,
• • twitching or rippling of the muscles in the face.

Eyes and vision

People with Azorean disease may experience double vision, bulging eyes, difficulty in looking upward, difficulty in opening the eyes, a fixed or staring gaze, or involuntary eye movements from side to side.

Other symptoms

Other symptoms reported in people with Azorean disease include difficulty in speech such as slurring, loss of feeling in arms or legs, frequent urination, infections of the lungs, diabetes, weight loss, and difficulty sleeping.