Congenital mitochondrial disorder of the metabolism of
ammonium (hyperammonemia) leading to an anomaly in the urea cycle.
Very rare; 37 cases from 24 families since 1981.
N-acetylglutamate is synthesized from acetyl-CoA
and l-glutamate by mitochondrial N-acetylglutamate synthetase (NAGS)
in the liver. Its role is to activate carbamoylphosphate synthetase, one of
the enzymes of the urea cycle. Impairment of the urea cycle produces
Elevated blood ammonium (NH4) level in a lethargic or
comatose patient. A liver needle biopsy is necessary to confirm the diagnosis.
Two clinical presentations, depending on complete
or partial lack of NAGS.
Neonatal Presentation: Starting within the first 4 days of life: refusal to drink, irritability,
persistent vomiting, and mild respiratory alkalosis, followed rapidly by
neurologic deterioration leading to coma, convulsions, and hypotonia.
Late-Onset Presentation: Long history of chronic hepatogastric symptoms, such as recurrent episodes
of vomiting, failure to thrive, and hepatomegaly. Others present a
neurologic picture of chronic encephalopathy, behavioral disorders
(agitation, delirium, irritability), or Reye-like syndrome following
valproate therapy for seizures. Death may occur during a metabolic crisis
precipitated by an infection, surgery, increased catabolism, or a protein-rich
diet. In case of seizures, sodium valproate should not be used because it
may precipitate acute metabolic decompensation. Liver transplantation is
curative. The basic treatment is a low-protein diet carefully calculated and
adapted to the child's needs and metabolic tolerance. N-carbamyl glutamate
can be given orally at a dose of 100 to 300 mg/ kg/day divided into three to
six doses, usually before feedings.
In case of hyperammonemia:
Stop protein intake and restrict fluid volume if there is any concern
about cerebral edema.
Provide a high-energy intake orally or intravenous (IV) (glucose 10-20%).
Use alternative pathways for nitrogen elimination: give sodium benzoate up
to 500 mg/kg/day, sodium phenylbutyrate up to 600 mg/kg/day, and l-arginine 300 mg/kg/day orally or IV. These drugs lead to
significant potassium losses, so potassium blood levels should be monitored.
Treat sepsis and convulsions aggressively.
Check blood glucose and NH4
levels. Make sure sodium benzoate, sodium phenylbutyrate, and l-arginine are available for emergency treatment of hyperammonemia.
Prolonged fasting should be avoided;
intravenous glucose (5 or 10% solution) should be administered to prevent
protein catabolism; monitor blood glucose, ammonium, and lactates level on
regular basis. Hypovolemia must be avoided, especially in patients with altered renal function.
If there is risk of nasal, pharyngeal, or gastric bleeding, a gastric tube
should be inserted to remove swallowed blood, which may provide a protein load
that may trigger acute metabolic decompensation. Prolonged postoperative
metabolic monitoring for early diagnosis of acute decompensation.
This sort of pathology should be
borne in mind when dealing with a supposedly “normal” child who does not
wake up after uneventful ...