Predisposition to Adult Onset Disease

Question 1

is ALS generally sporadic or familial?

Answer 1

• generally sporadic (1-2/100,000)
• 5-10% familial (AD + AR)
• mean age onset 55 years (younger in familial forms)

Question 2

ALS clinical features

Answer 2

• progressive muscle weakness, wasting and increased reflexes i.e. upper and lower neurone signs)
• limb and bulbar muscles involved
• pure motor signs (with fasciculations)
• cognition spared
• death due to respiratory failure

Question 3

what is the function of superoxide dismutase (SOD)?

Answer 3

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.

Question 4

what enzyme is involved with ALS?

Answer 4

• Cu/Zn superoxide dismutase (SOD), 20% of familial cases, 2% of all cases
• a ubiquitous enzyme, motor neurones express it highly
• could be a toxic gain of function? toxic intracellular aggregates?

Question 5

genetics of Huntington’s disease

Answer 5

• autosomal dominant
• adult-onset
• unique mutation identified … CAG expansion

Question 6

Huntington’s disease clinical features

Answer 6

Movement disorder:
- chorea
- athetosis
- myoclonus
- rigidity

Cognitive changes:
- poor planning and memory
- subcortical dementia (executive function)
- not classical dementia

Personality change:
- irritable
- apathetic
- loss of empathy
- disinhibition
- self-centred

Psychiatric disease:
- depression
- paranoia
- psychosis

Question 7

what are the possible advantages of predictive testing for Huntington’s disease for this lady?

Answer 7

• uncertainty of gene status removed
• if negative: concerns about self and offspring reduced
• if positive: make plans for the future, arange surveillance/treatment if any, inform children/decide whether to have children.

Question 8

what are the disadvantages of predictive testing for Huntington’s disease?

Answer 8

If positive:
- removes hope
- continues uncertainty (when)
- known risk to offspring
- impact on self/partner/family/friends
- potential problems with insurance/mortgage

If negative:
- expectations of a ‘good’ result
- ‘survivor’ guilt