Nitrogen 3 Flashcards
What is an inherited metabolic disorder?
Group of genetic diseases involving metabolic defects
How can the incidence of IEM be described?
Individually rare but collectively not uncommon
What is normally the cause of IEM?
Single gene defects
What do IEM usually result in?
Deficiencies of key enzymes
What do deficiencies of key enzymes result in?
Abnormal synthesis or catabolism of:
- Proteins
- Amino acids
- Carbohydrates
- Lipids
Describe the inheritance of IEM.
- Most show autosomal recessive inheritance
- Heterozygotes are phenotypically normal
What are some common clinical features of IEM presenting in childhood?
- Acidosis
- Failure to thrive
- Vomiting, refusal of feeds, irritability
- CNS dysfunction
- Hypoglycaemia
- Unusual odour
Where does the urea cycle take place?
It is split between mitochondrial matrix and cytosol
What are the 5 enzymes that catalyse the cycle in the liver?
- Carbamoyl phosphate synthetase
- Ornithine transcarbamoylase
- Argininosuccinate sythetase
- Argininosuccinate lyase
- Arginase
What is the regulatory enzyme in the urea cycle?
CPS1
Carbamoyl phosphate sythetase
What is the allosteric activator of CPS1?
N-acetyleglutamate
What is the most common urea cycle defect??
Ornithine transcarbamoylase deficiency
What is the genetics behind OTC deficiency?
It is the only X-linked inheritance. The 5 other disorders are autosomal recessive
What are the characteristics of OTC deficiency?
- Hyperammonaemia
- Presentation in newborns
How do amino acid disorders come about?
- Amino acids can be metabolised into other amino acids, hormones, pigments, neurotransmitters
- Enzymes play a key role
- IEM cause decreased enzyme activity
- Decreased product
- Increased precursors
- Alternative metabolic products
What is PKU?
-An autosomal recessive disorder which causes the absence/deficiency of phenylalanine hydroxylase
What are the clinical features of PKU?
- Near normal blood Phe at birth
- Rapidly rising Phe levels after feeding commences
- Irritability and feeding difficulties
- Delayed mental development and neurological features
- Musty odour
How is PKU diagnosed?
- Guthrie card
- Quantitative amino acid analysis
- Increase blood Phe and decreased blood tyrosine
- Dietary treatment commenced
What is the treatment for PKU?
-Low protein diet with protein substitute
-Blood Phe measured
Monitor vitamin and trace elements
