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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, and coma.

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Ornithine Transcarbamylase Deficiency.

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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 the blood.

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Approximately 1:80,000 live births. Estimated prevalence for disorders of urea cycle is approximately 1:30,000 population.

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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.

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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.

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Elevated blood NH4 level in a lethargic or comatose patient; liver biopsy; increased urinary orotic acid levels.

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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.

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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 protein-rich diet.

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In case of seizures, sodium valproate should not be used because it may precipitate acute metabolic decompensation. Liver transplantation is curative.

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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.

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In case of hyperammonemia:

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  • 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 ...

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