Predisposition to Adult Onset Disease Flashcards
when can children and adolescents be tested for adult onset diseases?
potential medical benefits
ALS: age
55 yrs
ALS: what % is familial?
5-10%
ALS: clinical features
- Progressive muscle weakness, wasting and increased reflexes
- (ie upper and lower neurone signs)
- Limb and bulbar muscles involved
- Pure motor signs (with fasciculations)
- Cognition spared
- Death due to respiratory failure
ALS: cause
• Cu/Zn superoxide dismutase (SOD):
~20% of familial cases, 2% of all cases
• 1y function: catalyses conversion of intracellular
superoxide radicals produced during normal
metabolism
• Ubiquitous enzyme, motor neurones express it highly
• ?toxic gain of function ?toxic intracellular aggregates
what is superoxide dismutase? (SOD)
The presence of SOD protects many types of cells from free
radical damage that is important in ageing and ischaemic
tissue damage
SOD also helps protect cells from DNA damage, lipid
peroxidation, ionising radiation damage, protein denaturation
………….. and other forms of progressive cell degradation
where is SOD1 found?
cytoplasm
where is SOD2 found?
mitochondria
where is SOD3 found?
extracellular
what SOD contains copper and zinc in its reactive centre
1 + 3
what SOD contains manganese in its reactive centre
2
on what chromosoms are the SOD genes located
21, 6, 4
huntington’s disease: inheritance
autosomal dominant
huntington’s disease: mutation
CAG expansion
huntington’s disease: clinical features
Movement Disorder: chorea athetosis myoclonus rigidity
- Cognitive changes:
- poor planning & memory
- subcortical dementia (executive function)
- NOT classical dementia
- Personality change
- Irritable
- Apathetic
- loss of empathy ‘A different person’
- disinhibition
- self centred
- Psychiatric disease:
- depression, paranoia, psychosis
