Rare genetic disorder characterized by complete or
partial lack of the enzyme ornithine transcarbamylase (OTC). Lack of the
enzyme results in excessive hyperammonemia, which is known as a neurotoxin.
Clinically, patients present vomiting, refusal to eat, progressive lethargy,
Ornithine Transcarbamylase Deficiency.
The urea cycle disorders are a group of rare disorders that
affect the urea cycle, a series of biochemical processes in which nitrogen
is converted into urea and removed from the body through the urine. Nitrogen
is a waste product of protein metabolism. Failure to break down nitrogen
results in the abnormal accumulation of nitrogen, in the form of ammonia, in
Approximately 1:80,000 live births. Estimated prevalence
for disorders of urea cycle is approximately 1:30,000 population.
Partially dominant X-linked (Xp21.1). The
phenotype of heterozygote females cannot be predicted because of random
inactivation of the X chromosome. Some female carriers present clinical
symptoms a few weeks after delivery, at the time of uterine involution.
Ornithine carbamoyltransferase is one of six
enzymes that play a role in the breakdown and removal of nitrogen in the body,
a process known as the urea cycle. The entire urea cycle resides exclusively in
periportal hepatocytes. It is an essential pathway for waste nitrogen
excretion. It is involved in a cascade of six enzymatic transformations
converting toxic ammonia to nontoxic water-soluble urea.
Elevated blood NH4 level in a lethargic or comatose
patient; liver biopsy; increased urinary orotic acid levels.
Neonatal Presentation: Starts within the first
4 days of life: refusal to feed, irritability,
persistent vomiting, mild respiratory alkalosis, followed rapidly by
neurologic signs with coma, convulsions, 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 such as agitation,
delirium, and irritability; or Reye-like syndrome following sodium valproate
therapy for seizures. Some patients spontaneously avoid protein-rich food
and remain relatively asymptomatic. Death may occur during a metabolic
crisis precipitated by infection, surgery, increased catabolism, or a
In case of seizures, sodium valproate should not be used because it may precipitate acute
metabolic decompensation. Liver transplantation is curative.
Basic treatment is a low-protein diet carefully adapted to the child's needs and metabolic
tolerance and administration of ammonia-scavenging drugs (Na-benzoate,
Na-phenylbutyrate, l-arginine) three to four times per day. Their
administration should be linked to meals to maximize their effect.
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 IV (glucose 10-20%).
Use alternative pathways for nitrogen elimination: give Na-benzoate up to
500 mg/kg/day, Na-phenylbutyrate up to 600 mg/kg/day, and l-arginine
300 mg/kg/day orally or IV. Because these drugs lead to ...