Huntington's disease Flashcards
what is the definition of huntington’s disease?
Huntington’s disease is a slowly progressive, neurodegenerative disorder characterised by chorea, incoordination, cognitive decline, personality changes, and psychiatric symptoms, culminating in immobility, mutism, and inanition.
what is the epidemiology of huntington’s disease?
35-45 age of onset
More common in north american and european ethnicities
what is the aetiology of huntington’s disease?
Autosomal dominant
Caused by an expanded CAG repeat at the N-terminus of the gene that codes for the huntingtin protein.
what are the risk factors for huntington’s disease?
Family history
Expansion of the CAG repeat length at the N-terminal end of the huntington gene
what is the pathophysiology of huntington’s disease?
The expanded CAG repeat generates an elongated polyglutamine tail on the huntingtin protein, which leads to cleavage and the generation of toxic fragments of this abnormal protein. The polyglutamine composition of the toxic fragments predisposes them to cross-link, forming aggregates that resist degradation and interfere with a variety of normal cellular functions, particularly mitochondrial energy metabolism. However, these aggregates also interfere with the regulation of transcription, axonal and vesicular transport, apoptosis, proteasome function, and cell-cell interactions. Haploinsufficiency, the reduction in levels of wild-type huntingtin, does not cause disease. However, it may contribute to the adverse effects of aggregates. Therapeutic interventions designed to improve mitochondrial function, block huntingtin cleavage at sites that generate toxic fragments, prevent expression of mutant huntingtin, improve cell-cell interactions, enhance autophagic consumption of mutant proteins, and retard apoptosis are under active investigation
Huntington’s disease primarily affects the striatum, and most clinical features are directly attributable to damage in this area, including cognitive impairment, behavioural changes, and loss of coordination. However, pathological changes occur in multiple cortical and subcortical structures as well.
Chorea, the most striking feature of Huntington’s disease, results from striatal dysfunction.
what are the key presentations of huntington’s disease?
Positive family history of huntington’s disease
Expanded CAG repeats at the N-terminus of the gene that codes for the huntingtin protein
Impaired work or school performance
Personality change
Irritability
Chorea - Random movements of fingers and toes, with occasional peculiar postures of hands, trunk, or limbs, and odd facial expressions are typical of early Huntington’s disease.
Twitching or restlessness
Loss of coordination
Deficit in fine motor coordinations
Slowed rapid eye movements
Motor impersistence impaired tandem walking
what are the signs of huntington’s?
Positive family history of huntington’s disease
Expanded CAG repeats at the N-terminus of the gene that codes for the huntingtin protein
what are the symptoms of huntington’s disease?
Impaired work or school performance Personality change Irritability Chorea - Random movements of fingers and toes, with occasional peculiar postures of hands, trunk, or limbs, and odd facial expressions are typical of early Huntington's disease. Twitching or restlessness Loss of coordination Deficit in fine motor coordinations Slowed rapid eye movements Motor impersistence impaired tandem walking
what are the first line and gold standard investigations for huntington’s disease?
CAG repeat testing - a positive result is ≥40 CAG repeats on 1 of the 2 alleles; an intermediate result is 36 to 39 repeats
Could do an MRI or CT - evident caudate or striatal atrophy may be apparent
what are the differential diagnoses for huntington’s disease?
Tardive dyskinesia
DRPLA
Neuroacanthocytosis
how is huntington’s disease managed?
Counselling, exercise programmes
Chorea - tetrabenazine or antipsychotics
Depression - antidepressants
Mood instability - anticonvulsants
Anxiety and insomnia - SSRIs or benzodiazepines
OCD - SSRIs, antipsychotics or clomipramine and CBT
how is huntington’s disease monitored?
Patients should be seen at 6- to 12-month intervals or more often as problems arise. Even if the visits are brief, the encounters are often useful for identifying career fatigue or critical loss of function
what are the complications of huntington’s disease?
Weight loss, dysphagia, falls, suicide risk, incontinence
what is the prognosis for huntington’s disease?
Many people with Huntington’s disease stay on antidepressants for the rest of their lives once treatment has been commenced. Chorea may lessen in severity in some patients with disease progression and, as such, occasional dose reductions in anti choreic therapy are warranted to see whether lower doses are effective or still needed. Behavioural problems may lessen or fluctuate as cognitive impairment worsens. Other symptoms of Huntington’s disease (e.g., dysphagia, dysarthria, impaired gait, cognitive dysfunction, and incoordination) are progressive.
