Huntington's Disease Flashcards
Definition of Huntington’s Disease
Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by the degeneration of specific nerve cells in the brain.
It is a autosomal dominantgenetic disorder caused by an inherited mutation in the huntingtin (HTT) gene.
It primarily affects the basal ganglia, a group of structures deep within the brain involved in movement control, cognition, and emotions.
Pathomechanism of Huntington’s Disease
Huntington’s disease is caused by a mutation in the HTT gene, which results in the production of an abnormal form of the huntingtin protein.
The mutated protein accumulates within neurons, leading to neuronal dysfunction and eventual cell death.
This progressive neurodegeneration primarily affects the striatum,and subsequently spreads to other areas of the brain.
The exact pathomechanism of Huntington’s disease is not fully understood, but it involves a complex interplay of cellular processes, including excitotoxicity, mitochondrial dysfunction, oxidative stress, impaired protein clearance, and altered neurotransmitter signaling.
Causes of Huntington’s Disease
Huntington’s disease is caused by an autosomal dominant mutation in the HTT gene. Individuals who inherit a single copy of the mutated gene from either parent will develop the disease.
The mutation involves the expansion of a specific DNA segment called CAG repeats within the HTT gene.
The greater the number of CAG repeats, the earlier the onset and more severe the symptoms of the disease.
Symptoms of Huntington’s Disease
Motor symptoms: Involuntary jerking or writhing movements (chorea), abnormal eye movements, muscle rigidity, and impaired coordination and balance.
Cognitive symptoms: Decline in cognitive functions, including difficulties with concentration, memory, and problem-solving. Executive function deficits and personality changes may also occur.
Emotional and psychiatric symptoms: Depression, anxiety, irritability, apathy, mood swings, and social withdrawal are common. Psychiatric symptoms, such as psychosis and obsessive-compulsive behaviors, can also occur.
Speech and swallowing difficulties: Slurred speech, changes in voice volume and pitch, and difficulty swallowing.
Diagnosis of Huntington’s Disease
Clinical assessment: Evaluating the individual’s medical history, symptoms, and physical examination to identify characteristic features of the disease.
Genetic testing: A blood test can detect the presence of the HTT gene mutation by analyzing the number of CAG repeats.
Neuroimaging: Magnetic resonance imaging (MRI) or positron emission tomography (PET) scans can help assess structural changes in the brain and detect patterns of neurodegeneration.
Differential diagnosis of Huntington’s Disease
Parkinson’s disease: Both diseases can present with movement abnormalities, but Huntington’s disease typically involves more prominent chorea and psychiatric symptoms.
Wilson’s disease: A genetic disorder that can present with movement abnormalities and psychiatric symptoms, but it often includes liver dysfunction and Kayser-Fleischer rings in the eyes.
Spinocerebellar ataxias: A group of genetic disorders that can cause movement abnormalities and cognitive decline, but they typically lack the characteristic chorea of Huntington’s disease.
Treatment of Huntington’s Disease
Medications:
Tetrabenazine and deutetrabenazine, can help manage chorea and other movement abnormalities.
Antidepressants, antipsychotics, and mood stabilizers may be prescribed to address psychiatric symptoms.
Physical therapy: Physical therapy can help maintain mobility, strength, and balance, and occupational therapy can assist with daily activities.
Speech therapy: Speech therapy aims to improve speech and swallowing difficulties.
Supportive care: Providing psychological support, counseling, and assistance with social and emotional challenges.
Complications of Huntington’s Disease
