Target Health Blog

Huntington's Disease

October 21, 2019


A montage of three images of single striatal neurons transfected with a disease-associated version of huntingtin, the protein that causes Huntington's disease. Several neurons colored yellow and having a large central core with up to two dozen tendrils branching out of them, the core of the neuron in the foreground contains an orange blob about a quarter of its diameter. Nuclei of untransfected neurons are seen in the background (blue). The neuron in the center (yellow) contains an abnormal intracellular accumulation of huntingtin called an inclusion body (orange). Studies using an automated microscope and survival analysis demonstrated that neurons with disease-associated huntingtin that form inclusion bodies survive longer than those that do not.
Graphic credit: by Dr. Steven Finkbeiner, Gladstone Institute of Neurological Disease, The Taube-Koret Center for Huntington's Disease Research, and the University of California San Francisco - Study Using Robotic Microscope Shows How Mutant Huntington's Disease Protein Affects Neurons. Press releases. National Institute of Neurological Disorders and Stroke (2004-10-13). Retrieved on 2009-03-15., CC BY 3.0,

Huntington's disease (HD), also known as Huntington's chorea, is an inherited disorder that results in the death of brain 1) ___. HD affects about 4 to 15 in 100,000 people of European descent. It is rare among Japanese, while the occurrence rate in Africa is unknown. The disease affects men and women equally. Complications such as pneumonia, heart disease, and physical injury from falls reduce life expectancy. Suicide is the cause of death in about 9% of cases. Death typically occurs fifteen to twenty years from when the disease was first detected.

The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unsteady gait often follow. As the disease advances, uncoordinated, jerky body movements become more apparent. Physical abilities gradually worsen until coordinated movement becomes difficult and the person is unable to talk. Mental abilities generally decline into dementia. The specific symptoms vary somewhat between people. Symptoms usually begin between 30 and 50 years of age, but can start at any 2) ___. The disease may develop earlier in life in each successive generation. About eight percent of cases start before the age of 20 years and typically present with symptoms more similar to Parkinson's disease. People with HD often underestimate the degree of their problems.

HD is typically inherited, although up to 10% of cases are due to a new mutation. The disease is caused by an autosomal dominant mutation in either of an individual's two copies of a 3) ___ called Huntingtin. This means a child of an affected person typically has a 50% chance of inheriting the disease. The Huntingtin gene provides the genetic information for a protein that is also called “huntingtin“. Expansion of CAG (cytosine-adenine-guanine) triplet repeats in the gene coding for the Huntingtin protein results in an abnormal protein, which gradually damages cells in the 4) ___, through mechanisms that are not fully understood. Diagnosis is by genetic testing, which can be carried out at any time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results. There is no cure for 5) ___. Full-time care is required in the later stages of the disease. Treatments can relieve some symptoms and in some improve quality of life. The best evidence for treatment of the movement problems is with tetrabenazine.

The first likely description of the disease was in 1841 by Charles Oscar Waters. The condition was described in further detail in 1872 by the physician George Huntington. The genetic basis was discovered in 1993 by an international collaborative effort led by the Hereditary Disease Foundation. Research and support organizations began forming in the late 1960s to increase public awareness, to provide support for individuals and their families, and to promote research. Current research directions include determining the exact mechanism of the 6) ___, improving animal models to aid with research, testing of medications to treat symptoms or slow the progression of the disease, and studying procedures such as stem cell therapy with the goal of repairing damage caused by the disease. Embryos produced using in vitro 7) ___ may be genetically tested for HD using preimplantation genetic diagnosis (PGD). This technique, where one or two cells are extracted from a typically 4- to 8-cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos affected with HD genes are not implanted, and therefore any offspring will not inherit the disease. Some forms of preimplantation genetic diagnosis - non-disclosure or exclusion testing - allow at-risk people to have HD-free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop HD. In exclusion testing, the embryos' DNA is compared with that of the parents and grandparents to avoid inheritance of the chromosomal region containing the HD gene from the affected grandparent. In non-disclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for HD are never disclosed. It is also possible to obtain a prenatal diagnosis for an embryo or fetus in the 8) ___, using fetal genetic material acquired through chorionic villus sampling. An amniocentesis can be performed if the pregnancy is further along, within 14-18 weeks. This procedure looks at the amniotic fluid surrounding the baby for indicators of the HD mutation. This, too, can be paired with exclusion testing to avoid disclosure of parental genotype. Prenatal testing can be done when a parent has been diagnosed with HD, when they have had genetic testing showing the expansion of the HTT gene, or when they have a 50% chance of inheriting the disease. The parents can be counseled on their options, which include termination of pregnancy, and on the difficulties of a child with the identified gene. In addition, in at-risk pregnancies due to an affected male partner, non-invasive prenatal diagnosis can be performed by analyzing cell-free fetal DNA in a blood sample taken from the mother (via venipuncture) between six and twelve weeks of pregnancy. It has no procedure-related risk of miscarriage (excepting via needle contamination).

Huntington's disease, particularly the application of the genetic test for the disease, has raised several ethical issues. The issues for genetic 9) ___ include defining how mature an individual should be before being considered eligible for testing, ensuring the confidentiality of results, and whether companies should be allowed to use test results for decisions on employment, life insurance or other financial matters. The development of an accurate diagnostic test for Huntington's disease has caused social, legal, and ethical concerns over access to and use of a person's results. Many guidelines and testing procedures have strict procedures for disclosure and confidentiality to allow individuals to decide when and how to receive their results and also to whom the results are made available. Financial institutions and businesses are faced with the question of whether to use genetic test results when assessing an individual, such as for life 10) ___ or employment.

The death of Woody Guthrie led to the foundation of the Committee to Combat Huntington's Disease. In 1968, after experiencing HD in his wife's family, Dr. Milton Wexler was inspired to start the Hereditary Disease Foundation (HDF), with the aim of curing genetic illnesses by coordinating and supporting research. At roughly the same time as the HDF formed, Marjorie Guthrie helped to found the Committee to Combat Huntington's Disease (now the Huntington's Disease Society of America), after her husband Woody Guthrie died from complications of HD. Sources: Wikipedia;

ANSWERS: 1) cells; 2) age; 3) gene; 4) brain; 5) HD; 6) disease; 7) fertilization; 8) womb; 9) testing; 10) insurance

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