Flashcards in Nitrogen 3 Deck (21)
Inherited metabolic disorders usually result in abnormal synthesis and catabolism of:
When are symptoms of an inherited metabolic disorder usually most severe?
Infancy or childhood
What type of inheritance pattern do IMD's follow?
Autosomal recessive inheritance
What are some of the most common clinical features of inherited metabolic disorders present in childhood?
Failure to thrive
Vomiting, refusal of feeds, vomiting
Central nervous system dysfunction
What happens to ingested protein that is surplus to the bodies needs? Why?
It is catabolised because there is no storage facility for excess proteins.
Where in the cell is the urea cycle?
It is split between the cytosol and the mitochondria
How many enzymes catalyse the reaction in the liver?
What does the concentration of the enzymes controlling the urea cycle depend on?
The quantity of protein in the diet
What is the regulatory enzyme in the urea cycle?
CPS1 - Carbomyl Phosphate synthase
What is the allosteric activator of CPS1? (Carbomyl phosphate synthase)
How many inherited disorders of the urea cycle exist?
Describe the inherited metabolic disorder associated with OTC?
Deficiency in ornithine transcarbamoylase
Present in 1 in every 40000 births in the UK
X - Linked, meaning the male is hemizygous to the gene mutation.
Characterised by hyperannomaenia which is elevated blood ammonia level - highly toxic
Usually present in newborn period
What may amino acids be metabolised into?
Other amino acids, hormones, neurotransmitters, pigments
What do inherited gene defects in the amino acid conversion pathway result in?
Decreased enzyme activity
Alternative metabolic products, potentially toxic
What enzyme is deficient or absent in phenylketonuria?
Phenylalanine hydroxylase (responsible for converting phenylalanine to tyrosine)
What type of inheritance is PKU?
Why are high levels of phenylalanine bad?
Toxic - can result in impaired brain development
What is the treatment?
Reduced protein diet wupplemented with tyrosine
What are the clinical features of PKU?
Normal Phe levels at birth, Phe levels rise rapidly once feeding is introduced
Days 3 and 4 may present feeding difficulties
Delayed mental development and neurological features are present by 6 months of age
How is diagnosis achieved of PKU?
Positive screening test
Quantitive amino acid analysis
Confirmation of increased blood Phe levels
Typically a decrease in blood tyrosine levels