Ornithine transcarbamylase (OTC) deficiency is the most common inherited disorder
of the urea cycle (prevalence range from 1 in 40,000 to 1 in 80,000). It is inherited
in an X-linked manner and classically presents with early episodes and severe progression
in males. The clinical phenotypes in carrier females show a widely spread presentation
also inside an affected family and are depending on X-inactivation status in the liver.
We report on a 7 year old girl with normal psychomotoric development to date, who
presented with vomiting for 2 days and progressing agitation, dysarthria, mydriasis,
intermittent drowsiness and disorientation.
The symptoms had started 3 hours after the last (and before recurrent) application
of dimenhydrinate. There were no signs of hypoglycemia, serum electrolyte disturbance,
an intracranial lesion (CT-scan) or meningitis (lumbar puncture), supporting the diagnosis
of dimenhydrinate intoxication with typically central nervous system symptoms for
young age (new-onset psychosis and agitation) and anticholinergic signs like urinary
retention.
Her further history evaluated intermittent episodes of nausea and vomiting for 9 months,
previously diagnosed as chronic gastritis. At presentation she was hyperammonemic
(maximum of 260µmol/l) suggestive of urea cycle defects. She was initially treated
with dextrose infusions, protein restriction and intravenous sodium benzoate.
Plasma amino acid analysis revealed an increased glutamine and low citrulline and
she had an elevated urinary orotate indicating an ornithine transcarbamylase deficiency.
DNA mutation analysis identified a heterozygous mutation R92Q (c.275G>A) in the OTC-gene
as spontaneous mutation. She was discharged on a protein-restricted diet with supplementation
of essential amino acids and treatment with sodium benzoate, sodium phenylbutyrate
and citrulline and is going on well.
Even if only 10 percent of female carriers for an OTC deficiency will become symptomatic,
a partial OTC deficiency should be considered in the differenzial diagnosis of unexplained
acute encephalopathy, especially in girls. An early diagnosis and resulting therapy
in time is essential for the long-term neurological outcome.
