Term
| What is the genetic inheritance and basic pathophysiology of Huntington's Disease? |
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Definition
1) Autosomal dominant with high penetrance (worse from Dad, with sperm instability of repeat)
2) Degeneration of neurons in Striatum (mainly), cortex, hippocampus and hypothalamus caused by CAG expansion of huntington protein (Polyglutamine tail) |
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Term
| Which cells are vulnerable to Degeneration in HD, and which types are resistant? |
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Definition
Remember, distribution of mutant huntington does NOT explain neuronal damage
1) Medium spiny, projecting neurons that use Enkephalin and Substance P are very sensitive
2) Large spiny, intrinsic neurons that use ACh and medium spiny, intrinsic neurons that use NO are resistant. |
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Term
| What features define HD pathogenesis? |
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Definition
1) Protein Aggregation/Intracellular inclusion
- longer repeat, younger onset, more aggregation
- soak up transcription factors important for proteolysis
2) Mitochondrial impairment
- Calcium handeling and Apoptosis de-regulated
3) Excitotoxicity
- NMDA-mediated, calcium-induced toxicity
4) Transcriptional dysregulation
- HDAC is a target |
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Term
| How is HD diagnosed clinically? |
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Definition
Gene Test (Confirmatory, Predictive and Prenatal)
- Unaffected children at risk are NOT TESTED
1) CAG <=26 are normal
2) 27-35 are not at risk, but child might be
3) 36-39 is uninformative
4) >=40 will get it, with >60 causing juvenile |
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Term
| How is Juvenile-onset HD distinguished from adult-onset HD? |
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Definition
| Juvenile form exhibits less Chorea and more Bradykinesia (Parkinsonian) |
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Term
| How is Juvenile HD usually identified? |
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Definition
| Sudden, erratic behavioral changes and School failure, with Bradykinesia. |
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Term
| What clinical features define HD? |
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Definition
1) Movement
- Slow Saccades (Early)
- Chorea incorporated into normal movements
- Dystonia and Bradykinesia (LATE) (dysphagia, facial expression loss and postural issues)
2) Emotional
- Depression and Personality changes (violent and/or angry)
3) Cognitive Decline |
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Term
| What treatments are available for HD and how are they often utilized? |
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Definition
1) Tetrabenazine (DA depletion) blocks chorea but causes side effects and does not imporve overall motor symptoms
2) Neuroleptics (DA-R antagonists) are ONLY used for Psychosis associated with HD. |
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