Huntington's Disease Overview


Huntington's disease is a hereditary, progressive neurodegenerative disorder that mainly affects the brain's basal ganglia; it is caused by a mutation in a gene located on chromosome 4 that codes for a protein called Huntingtin, also known as Htt. 

 The type of mutation that produces this disease is an expansion of CAG triplets, which results in the Huntingtin protein having an enormous size, which interferes with the normal functions of neurons and acts by facilitating their death by different mechanisms; among them is the formation of aggregates.

This disease is inherited with an autosomal dominant character; each child of an affected father or mother has a fifty percent (50%) probability of inheriting this disease. The age of onset of symptoms is highly variable but, on average, usually ranges between thirty (30) and fifty (50) years of age. The juvenile form of the disease appears early between childhood and adolescence, and the late form can occur after age 70.

It is unknown how many people are currently affected by this disease. It is considered underdiagnosed since many countries lack the resources to rule out the mutation in patients with movement disorders. However, it is estimated that about 30,000 sick people in the United States and about 150,000 are at risk of developing it. Huntington's disease equally affects all races and ethnic groups and affects both sexes equally.

Barranquitas, a town near Lake Maracaibo in Venezuela, has the most significant cases of this disease globally. In this place, samples were obtained for detecting the mutation in the gene that causes the disease in 1993 by a group of researchers led by Dr. Nancy Wexler, whose mother suffered from this disorder.

In most cases, patients experience cognitive symptoms as well as motor symptoms. Dementia, depression, delusions, mania, and mood disorders affect them.

"Mal de San Vito" is a popular term for involuntary choreic movements—instability of gait; difficulty maintaining balance, which results in frequent falls.

Dysphagia, or difficulty swallowing food, produces significant weight loss and malnutrition, together with the high energy expenditure that these patients have.

Lastly, patients die not from the disease but from complications arising from a weakening immune system and body. Generalized infections, pneumonia, and cardiac disorders, including arrhythmias, are some examples of these complications.

Three fundamental elements go into the diagnosis: clinical history, family history, and molecular genetic test.

There are currently no treatments for this disease despite the multiple ongoing clinical trials; however, biotechnology such as siRNA, antisense oligonucleotides, and mesenchymal stem cells are also being studied as methods of silencing the gene that encodes the mutated protein.

Marta Talise, MD.