Week 10 - Inborn Error of Metabolism Flashcards
1
Q
How are glycogen storage disorders diagnosed?
A
- present with fatigue upon exercise
- lack of glycogen
- relatively mild phenotype
2
Q
How are glycogen storage disorders treated?
A
- dietary interventions
- maintain glucose availability in between meals or during exercise
- this can cause diabetes
- frequent administration of cornstarch
- to provide complex carbohydrates to be converted into glucose
3
Q
Why can’t gene therapy treat glycogen storage disorders?
A
- can be risky
- not worth treating only mild symptoms
- all genes have to be targeted
4
Q
How is cystic fibrosis diagnosed?
A
- newborn blood spot
- presence of trypsin
- triggers genetic test
- causes build up of sticky mucus in lungs and pancreas
- affects breathing and digestion
- lung infections due to mucus not moving
5
Q
What are the genetics of cystic fibrosis?
A
- affects CFTR gene
- encodes plasma membrane anion transported
- of ABC (ATP Binding Cassette)
- expressed in epithelial cells
- reduces channel activity or expression
6
Q
What is the biochemistry of cystic fibrosis?
A
- chloride export causes water to follow by osmosis
- thins mucus
- mucus can move
- defective export leads to thick mucus
7
Q
What is the treatment of cystic fibrosis?
A
- physiotherapy
- exercise
- breathing techniques
- help move mucus in lungs
- digestive enzyme capsules for pancreatic insufficiency
- lung transplants
8
Q
Why is gene therapy a suitable treatment for cystic fibrosis?
A
- single gene disorder
- loss of function means CFTR expression should be therapeutic
- expression does not need to occur in all cells
- lung epithelium is accessible by nebulisers (unless late treatment)
9
Q
How is PKU diagnosed?
A
- PhenylKetonUria
- newborn blood spot
- high levels of phenylalanine
- causes damage to brain and nervous system
10
Q
What is the genetics of PKU?
A
- PAH (PhenylAlanine Hydrolase) affected gene
- missense mutation
- some nonsense and splicing mutations
11
Q
What is the biochemical consequence of PKU?
A
- lack of PAH means phenylalanine is not converted into tyrosine
- variant PKU from defected co-factor regeneration by dihydrobiopterin reductase
- accumulation of phenylalanine
- depletion of tyrosine
- both neutral AAs
- neutral AAs compete for cellular uptake by LAT1
- excess phenylalanine reduces uptake of other AAs
- lack of these affect brain development
- low tyrosine leads to lack of melanin
12
Q
What is the treatment of PKU?
A
- dietary restriction of phenyalanin
- low protein
- dietary supplementation of tyrosine
- treatment within 2 weeks allows normal brain development
13
Q
How are LSDs diagnosed?
A
- Lysosomal Storage Diseases
- white blood cell enzyme assays
- genetic tests
14
Q
What are the genetics of LSDs?
A
- many are autosomal
- some X-linked
- carrier female can also be diseased
- due to only some regions of each chromosome being expressed
- overall expression of 1 chromosome
- can include mutated region
15
Q
What is the treatment of LSDs?
A
- no cure
- deficient enzymes cannot be replaced as all cells would need to be targeted
