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Detailed information of HYPERAMMONEMIA
HYPERAMMONEMIA
DEFINITION:
A heterogeneous group of disorders characterized by elevated
ammonia in the blood resulting in altered levels of consciousness
and/or persistent vomiting.
EPIDEMIOLOGY:
- incidence: rare
- age of onset:
- risk factors:
DIFFERENTIAL DIAGNOSIS:
- Carbamoyl Phosphate Synthethase (CPS) Deficiency
- Ornithine Transcarbamylase (OTC) Deficiency
- Citrullinemia
- Argininosuccinic Aciduria
- Argininemia
2. Transient Hyperammonemia of the Newborn
2. Secondary
- Methylmalonic Acidemia
- Propionic Acidemia
- Isovaleric Acidemia
2. Fatty Acid Oxidation Defects
3. Reye's Syndrome
PATHOGENESIS:
- catabolism of nitrogenous compounds (endogenous and
exogenous proteins) produces amino acids which are further
metabolized to ammonia
- as ammonia is toxic to cells, the liver is the primary organ
for maintaining plasma ammonia levels <40 uM
- the liver eliminates ammonia by 2 routes:
- conversion of glutamate to glutamine
- conversion of ammonia to urea via the urea cycle
- assessment of hyperammonemia due to a urea cycle defect (hyperammonemia
+ normal anion gap), begins with the assessment of the 3rd
enzyme in the urea cycle (argininosuccinate synthe-tase); a
defect in this enzyme will result in an elevation of citrulline
- this initial assessment is followed by an assessment of the
4th and 5th enzymes of the urea cycle (argininosuccinate lyase,
arginase); a defect in these enzymes will result in a moderate
elevation of citrulline
- an assessment of the 1st and 2nd enzymes of the urea cycle (carbamoyl
phosphate synthetase, ornithine transcarbamylase) is last; a
defect in these enzymes will result normal or low citrulline
levels
CLINICAL FEATURES:
- usually normal at birth with onset of features 24-72 hours
after feeding (protein load) commences:
- lethargy -> coma
- infantile hypotonia
- neonatal seizures
2. Gastrointestinal Manifestations
- persistent vomiting (+/- dehydration)
- poor feeding
- hepatomegaly
3. Others
- hyperventilation (due to a respiratory alkalosis)
- hypothermia
2. Childhood
- usually present after a sudden protein load or an
inter-current infection with recurrent episodes of:
- lethargy -> coma
- acute ataxia
- hyperactivity
2. Gastrointestinal Manifestations
- persistent vomiting (+/- dehydration)
- hepatomegaly
INVESTIGATIONS:
- venous hyperammonemia (normal <40 uM)
- primary (>500 uM); secondary (<200 uM)
- blood gas, electrolytes
- check urine for organic acids (Organic Acidopathies,
Fatty Acid Oxidation Defects)
2. If anion gap normal:
- check plasma amino acids for
2. Urine
MANAGEMENT (Urea Cycle Defects):
- chronic diseases with a life-long risk of episodes of
hyperammonemia and thus must:
- provide long-term follow-up
- moniter ammonia levels
- coordinate a multidisciplinary approach:
- Paediatrics, Neurology, Dietary, Genetics, Metabolics
- plan for acute episodes
2. Goals of Therapy
- symptomatic control of and avoidance of acute episodes
- not curative
3. Diet
- IV D10W (during an acute episode)
- Mead Johnson 80056 Formula
- non-protein containing formula
- supplement with citrulline or arginine
2. Endogenous
- High Caloric Diet
- use to avoid or during an acute episode to minimize
tissue catabolism and thus the breakdown of endogenous
protein
4. Convert Nitrogen to an Excretable Compound
- conjugates with glycine and excreted as hippuric acid
2. Sodium Phenylacetate
- conjugates with glutamine and excreted as phenylacetyl-glutamine
3. Dialysis
- Peritoneal or Hemodialysis
5. Prognosis
- 100% mortality if untreated
- there is a direct correlation between the duration of hyper-ammonemic
coma and morbidity (mental retardation, developmental delays,
cortical atrophy)
- good prognosis if disorder is treated prospectively from
birth
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Pediatric Database - HYPERAMMONEMIA
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