Differenzial diagnosis of acute encephalopathy: Acute decompensation in ornithine transcarbamylase (OTC) deficiency in a seven year old girl

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.