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Flashcards in Nitrogen 3 Deck (9)
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1
Q

What are inherited metabolic disorders?

A

-Group of genetic diseases involving metabolic defects.
-Individually rare, but collectively not uncommon
-Typically result in deficiencies of key enzymes.
-Results in abnormal synthesis or catabolism of:
Proteins
Amino acids
Carbohydrate
Lipids
- Clinical symptoms usually severe and typically present in infancy or childhood.

2
Q

Effects of enzyme defects

A
  • Decreased formation of final product.
  • Accumulation of first 2 substrates
  • Increased formation of other metabolites.
3
Q

What are some common clinical features of inherited metabolic disorders presenting in childhood?

A
  • Acidosis
  • Failure to thrive
  • Vomiting, refusal of feeds, irritability.
  • Central nervous system dysfunction
  • Hypoglycaemia
  • Usual odour
4
Q

The Urea Cycle

A
  • Cycle is split between mitochondrial matrix and cytosol
  • 5 enzymes catalyse the cycle in the liver and their concentrations increase or decrease in response to high or low protein diets.
  • CPS1 is the regulatory enzyme
  • N-Acetylglutamate is allosteric activator of CPS1.
5
Q

Urea Cycle defects

A

6 inherited disorders of the urea cycle
Most common is ornithine transcarbamoylase (OTC) deficiency
- OTC has X-linked inheritance, rest are autosomal recessive.
- Characterised by hyperammonaemia (elevated blood ammonia level)-highly toxic
- Elevated blood ammonia is a medical emergency.
-Typically presents in newborn period.

6
Q

Amino acid disorders

A
  • Amino acids may be metabolised into other amino acids, hormones, pigments, neurotransmitters.
  • Enzymes play a key role in these processes.
  • Inherited gene defects cause decreased enzyme activity.
  • Decreased product
  • Increased precursors
    Alternative metabolic products (potentially toxic).
    Know PKU
7
Q

Phenylketonuria (PKU)

A
  • Absence/deficiency of Phenylalanine hydroxylase (PAH) - classical PKU
  • Autosomal recessive disorder
  • Associated with increased phenylalanine (Phe) levels (toxic)
  • Untreated individuals exhibit signs of impaired brain development.
  • Treatable condition - Reduced protein diet supplemented with tyrosine.
  • Neonatal screening programme (carried out on day 5).
8
Q

Phenylketonuria (PKU) - Clinical features

A
  • Normal at birth with near normal blood Phe levels.
  • Phe levels rise rapidly once feeding is established.
  • Days 3-4 may present with irritability and feeding difficulties.
  • If untreated, delayed mental development and neurological features are evident by 6 months of age.
  • Musty odour
9
Q

Phenylketonuria (PKU) - Treatment

A

-Low protein diet supplemented with “protein” substitute.
_maintain blood Phe levels between 120-360 umol/l
-Blood Tyr maintained at upper limit of reference range.
- Monitor vitamin and trace element status.
- Managed by multi-disciplinary team: Dietitians, metabolic physicians, biochemists, genetic counselling.