Huntington Disease presentation for medical students

Huntington diseases slides

1. Huntington’s quest: Solving the mystery of genetic enigma

2. The Enigma Unveiled (Patient History) A 40 year old male chef walked in an ER after he got a cut on thumb while working in a kitchen. The physician stitched his wound. He was stumbling and had difficulty with his upper limb co-ordination. He told that he had a difficult time at work using his knife recently. He was noticed to have a short temper as he got in a fight with the patients in the waiting room.

3. Unraveling the clues (Clinical Features) SOURCE: https://youtu.be/8lItaU0ftK8 NeurosSocial ( youtube )

4. Cognitive Symptoms

5. THE QUEST BEGINS GENERAL PHYSICAL EXAMINATION

6. GAIT ATAXIA SORCE: https://gfycat.com/AdventurousDisfiguredFossa

7. CHOREIFORM MOVEMENTS

8. DYSTONIA

9. THE PUZZLE PIECES DIFFERENTIAL DIAGNOSIS

10. DIFFERENTIAL DIAGNOSIS Parkinson’s disease Wilson’s disease Spinocerebellar disease Huntington’s disease

11. PARKINSON’S DISEASE

12. WILSON’S DISEASE

13. SPINOCEREBELLAR ATAXIA

14. HUNTINGTON’S DISEASE

15. UNLOCKING GENETIC CODE GENETIC TESTING

16. PCR MECHANISM ECHANISM: Source:https :// youtu.be / eNTkEuvCmKM

17. SIGNIFICANCE: Synthesis of mutant DNA in sufficient quantities Comparison of mutant gene with normal gene RESULT: Presence of an expanded CAG repeat In the Huntington gene.

18. Imaging studies

19. Pathology Examination Autosomal dominant Huntingtin protein abnormality Chromosome 4 CAG repeats that code that for the amino acid glutamine

20. DISTORTIONAL MOVEMENTS

21. DEMENTIA

22. Biochemical Puzzle It’s a genetic neurological disorder  Caused by repeated expansion of CAG trinucleotides  Causing instability in the N-terminal of gene So there’s mutation in the gene Leads to the formation of unstable huntington protein  Protein misfolds and form aggregates

23. Excitotoxicity Mutant protein disrupts the calcium homeostasis   Release of excitatory neurotransmitter Leading to neuronal excitotoxicity Oxidative stress Neuronal damage

24. Neurotransmitter Imbalance There’s depletion of GABA and dopa Dysregulation of glutamate signaling Contributes to movement disorders and psychiatric disorder

25. Biomarkers Mutant huntingtin protein fragments, Neurofilaments light chain ( NfL ), and Specific metabolites in cerebrospinal fluid or blood 

26. Therapeutic Strategies

27. Medications Dopamine depleting drugs Antipsychotics Antidepressants

28. Physical & Occupational Therapy Speech & Language Therapy

29. Supportive Care Genetic Counselling & Testing

30. Research Investigational drugs for investigating and understanding HD Slow rate of progression of HD Block effects of excitotoxins Support factors that improve neuronal health Suppress metabolic defects

31. SUMMARY Autosomal Dominant Disease Affects 50% offspring of an affected individual Effects cerebral nerve tissue and basal ganglia Results from single defective gene on chromosome 4 Symptoms include: Choreiform movements Progressive dementia Gait Ataxia Treatment is symptomatic-no cure

32. THANKYOU