Lecture 10: Huntington’s disease Flashcards
Huntington’s disease
Sandra K. Kostyk, M.D., Ph.D.
Who was George Huntington?
George Huntington grew up on Long Island where both his father and grandfather had been physicians and had treated and followed members of several families over several generations.
George Huntington moved to Ohio and presented the first concise description of what became known as Huntington’s Disease at a medical conference in Pomeroy, Ohio in 1872.
Famous People who had Huntington’s Disease
From: Woody Guthrie: A Life by Joe Klein, 1980
Father Woody and Daughters Sue and Gwen had HD.
2 types of Huntington’s
Adult onset
Juvenile onset
HD basics
Autosomal dominant: there is a 50/50 chance of a child getting the disease if a parent has it.
HD does not skip generations:
If a person with an affected parent escapes the disease, so will all of their children.
HD is a trinucleotide repeat disorder.
(other repeat disorders include: Fragile X, Myotonic dystrophy, Kennedy’s, SCA I, Machado-Joseph, etc)
Individuals with >37 CAG (polyglutamine) repeats express the HD phenotype.
Repeat sizes from 27-36 are considered unstable for future generations. There is a tendency for “anticipation” when the gene is transmitted by the father.
There is a rough correlation between repeat size and age of onset.
anticipation
The progressively earlier appearance and increased severity of a disease from generation to generation. The phenomenon of anticipation was once thought to be an artifact, but a biological basis for it has been discovered in a number of genetic disorders, such as myotonic dystrophy and Huntington disease.
Occurrence (as of a disease or symptom) before the normal or expected time
Huntingtin is normally a
cytoplasmic protein
The disease starts insidiously and progresses continuously.
The HD CAG expansion causes a number of metabolic changes.
People with HD have decreased body mass index and over 3 years gain less weight than average Americans.
Increased 24 hr energy expenditure by11%.
Mitochondrial energy deficit found in muscle biopsy samples from pre-symptomatic and symptomatic people with HD gene expansion.
Cholesterol metabolism is abnormal in HD brain cells.
Altered glucose tolerance in people with HD, diabetes in HD mice.
HD brain
Caudate Loss in HD
Juvenile HD: Also includes
Globus pallidus and cerebellar involvement.
HD Symptoms include changes in:
Behavior
Motor function
Cognitive function
In adults, motor symptoms
include:
Chorea Motor impersistence Oculomotor changes Impaired fine motor control Balance and gait disorder Dystonia Speech/swallowing problems
Chorea
Chorea is a condition that causes involuntary, unpredictable body movements that do not have a pattern. Chorea symptoms can range from minor movements such as fidgeting to profound, uncontrolled movements of the arms and legs.
Dystonia
Dystonia is a disorder characterized by involuntary muscle contractions that cause slow repetitive movements or abnormal postures. The movements may be painful, and some individuals with dystonia may have a tremor or other neurologic features. There are several different forms of dystonia that may affect only one muscle, groups of muscles, or muscles throughout the body. Some forms of dystonia are genetic but the cause for the majority of cases is not known.
ViBE
The effect of Video game Biofeedback modulated Exercise on HD subjects on cognitive and physical symptoms.
- -Used a Variation of Dance Dance Revolution.
- -20 subjects enrolled. Two sessions per week for 6 weeks. Hand held video game control group.
Walking improved. Improved double support time, heel to heel base of support, stride length and velocity. Improved dynamic balance. Trend towards improvement in neuropsychiatric test measures.
Intellectual Difficulties In HD
Completing complex tasks Organizing and prioritizing Adapting to change Problem solving Creative thinking Word finding Memory problems
