Inborn Errors Of Metabolism Flashcards
What are inborn errors of metabolism?
Single gene defects resulting in disruption to metabolic pathways e.g. causing blockage of enzyme in pathways such as synthesis/catabolism of proteins, carbs etc..
What are the effects of IEM causes by?
- Toxic accumulation of substrates
- Toxic accumulation of intermediates from alternative metabolic pathways
- Defects in energy production due to deficiency of products
Name 4 IEM disorders?
Alkaptonuria
Cystinuria
Albinism
Pentosuria
How do IEM’s form? !!
CONGENITAL (present from birth)
INBORN (transmitted through gametes)
What type of disease is alkaptonuria?
Autosomal recessive disease
- congenital
What symptoms show in alkaptonuria?
Urine turns black when standing (+ alkanisation)
Black ochrotic pigmentation of cartilage and collagenous tissue
Which molecule is deficient in alkaptonuria?
Homogentisic acid oxidase deficiency
What is the one gene one enzyme concept?
Each biochemical reaction is under ultimate control of different single gene. Mutation of a single gene to a single enzyme in a metabolic pathway results in alteration of ability of cell to carry out single primary chemical reaction.
What is the molecular disease concept?
Evidence that human gene mutations result in altered primary structure in proteins. Inborn errors of metabolism are caused by mutations in genes that produce abnormal proteins
What are the 4 mechanisms of inheritance?
Autosomal recessive Autosomal dominant X-linked Mitochondrial - other environmental factors can also affect onset of disease
Which of the 4 mechanisms of inheritance is the most common?
Autosomal recessive
- autosomal dominant is rare
Give examples of autosomal recessive IEM diseases?
PKU (Phenylketonuria), alkaptonuria and MCADD
How does autosomal recessive disease arise?
Both parents carry a mutation affecting the same gene
What increases the risk of autosomal recessive disease?
1 in 4 risk each pregnancy is both parents carry mutation affecting same gene
- consanguinity increases risk
Give examples of autosomal dominant IEMs?
Marfan’s, acute intermittent porphyria
What are the chance of inheriting autosomal recessive vs autosomal dominant?
25% since both parents have to carry (50% chance of child being carrier instead)
50% chance for autosomal dominant (only one parent needs to carry)
How are X linked conditions passed on?
Maternal line - no male to male transmission (females carry by pass it one, males manifest but don’t pass on)
Who does X linked conditions appear in?
Males
Females carry unless lyonisation (random inactivation of one of X chromosome)
Give examples of X linked conditions?
Fabry’s disease
Ornithine carbomoyl transferase deficiency
What are mitochondrial disease caused by?
Mutations in mitochondrial gene (in the mtDNA not in normal DNA)
How is mitochondrial disease passed on?
Only eggs contribute mitochondria so only females pass on mitochondrial mutaition, males cannot pass it on but BOTH male and female offspring affected (no one carries)
What type of disease are mitochondrial disease - why is it not good?
Chronic genetic disorder
- cannot produce enough energy for body to function properly
Examples of mitochondrial disease
MERFF - myoclonic epilepsy and ragged red fibre disease (deafness, dementia and seizures)
MELAS - mitochondrial encephalopathy with lactic acidosis and stroke like episodes
What is heteroplasmy?
Cell contains varying amounts of normal mt DNA and also mutated mt DNA during mt DNA replication and cell division
