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Background and overview to inborn errors of metabolism (Hyperammonaemia…
Background and overview to inborn errors of metabolism
Testing: Biochemical
Quick and fast in order to be able to act quickly
High performance liquid chromatography
3 types of metabolic disorders
Disorders resulting in intoxication
IEM of intermediary metabolism
Normal embryo-fetal development
Symptom free interval after birth
Clinical signs of intoxication
Decompensation triggered by catabolism, food intake etc.
Most are treatable
Disorders:
Aminoacidopathies
Organic acidurias
Urea cycle defects
Sugar intolerances
Metals
Porphyrias
Neurotransmitters
Disorders of energy metabolism
Main target organs (liver, heart, muscle, brain)
Embryo-fetal development
Decompensation can be triggered by intercurrent infection, food intake
Diagnosis is difficult
Only few are amenable to treatment
Disorders of complex molecules
Defects in degradative enzymes
glycosaminoglycans
Defect in synthetic or processing enzyme
CDG, peroxisomal disease, cholesterol
Possible interference with embryo-fetal development
Not liable to decompensation
Manifestations are permanent, progressive, dependent upon diet
Storage disorders
Specific diagnostic methods
Treatment with enzyme replacement and substrate reduction
Hyperammonaemia
Always consider hyperammonaemia in unexplained encephalopathy
All acute hospitals should be able to accurately measure blood ammonia urgently
Normal levels 20-30
Urea cycle disorders >1500
Sources of ammonia
Catabolism of N containing molecules
Amino acids
Amines
Purines and Pyrimidines
Production within the small intestine, muscle and renal tubules
Emergency management
Supportive care
Removal of toxic metabolites
Na benzoate
Na phenylbutyrate
Arginine
Dialysis
Replenish depleted products
Prevent load on affect pathways
Long term management
Reduce load on affected pathway
Protein restriction
Prevent catabolism
Remove excess nitrogen
Replenish depleted products
Arginine
Menke Disease
Affects processing of copper
Broken/brittle hair
Cold, floppy baby with FTT
Seizures at ~3 months
PKU
Faulty PAH enzyme
High levels phenylalanine lead to severe DD and fits
Low levels of tyrosine leads to low melanin and fair hair/blue eyes