1. Inborn Errors of Metabolism: Perspectives from Metabolic Physician, Paediatric Intensivist and Nephrologist
8th International Conference
Paediatric Continuous Renal Replacement Therapy
London 18th July
Dr Mike Champion
Department of Inherited Metabolic Disease,
Evelina London Children’s Hospital

2. Ammonia

3. Ammonia Differential Diagnosis
Infection
eg proteus, klebsiella
Herpes simplex
Liver failure
Protein load & catabolism
eg trauma, burns
GI bleed
Chemotherapy
Portosystemic Shunt
Drugs
Valproate
Carbamazepine
Inborn Errors of Metabolism
Urea Cycle Defects
Enzymes eg OTC deficiency
Transport eg LPI, HHH
Organic Acidaemias
Fat Oxidation Defects
Pyruvate Carboxylase defciency
OAT deficiency (neo/infants)
HIHA
Transient Hyperammonaemia of the Newborn

4. Hyperammonaemia & RRT Rare problem UK 215 UCDs (10 yrs)
17% neonatal cases dialysed (40% died)
Chakrapani 2009
US 299 UCDs (25 yrs)
60% neonatal cases dialysed , 7% older cases dialysed
Enns 2007
Birmingham 14 neonatal cases in 10yrs requiring CVVH
Westrope 2010

5. Mortality/Morbidity UK n=215 UCDs (10 yrs)
36% mortality, 78% disability neonatal presentation
14% mortality, 56% disability overall
Chakrapani 2009
US n=299 UCDs (25 yrs)
32% mortality
16% mortality overall Enns 2007
Ammonia Team, Stanford n=11
Neonatal UCD mortality 9%
Enns 2009

6. Related to peak ammonia + duration
Prognosis
Related to peak ammonia + duration
If peak ammonia > 350mmol/l significant CNS deficits
n=108 UCDs Uchino 1998
Good outcome if ammonia < 250mmol/l or coma resolved
<48 hrs of onset symptoms n=12 UCDs Walter 2000
More likely to die if coma or ammonia >1000mmol/l
Better outcome if ammonia <500mmol/l n=299 UCDs Enns 2007
Peak ammonia >200mmol/l within first 48 hrs
independent risk factor for mortality (esp liver failure) n=90 UCD or LF
Ozanne 2011