Fatal initial adult-onset presentation of urea cycle defect

Lien J, Nyhan WL, Barshop BA. Arch Neurol 2007; 64:1777-1779.
Ornithine transcarbamylase (OTC) deficiency more commonly occurs in neonates,but can occur in adults. It leads to elevations in ammonia, encephalopathy and coma due to cerebral edema, and death. It is treatable (if diagnosed) with hemodialysis, intravenous arginine, and sodium benzoate/phenylacetate.
In this case report, a 20 yo presented to UCSD with metabolic disease 7 months after her father sudenly became hyperammonemic and died at 52. She had NO other family or personal medical history of prior episodes, and exam was normal. Her father awaoke 8 days after surgery for a throat polyp confused and combatative, developed seizures and had ammonia of 4202. He had cerebral edema and punctate pontine hemorrhages at autopsy.

The daughter later became pregnant with twins, and amniocentesis showed a mutation in both fetuses. She was then admitted given oral citrulline and a low protein diet. The first baby was delivered at 33 weeks vaginally, subsequently intubated, treated with a low protein diet, iv arginine and oral citrulline one he tolerated enteral feedings and did well.

The second baby also had perinatal problems but was treated as above and did well, both discharged at 6 weeks on low protein diets and citrulline and remained healthy.

The differential of the high ammonia in the father included disorders of fatty acid oxidation of organic acidemias. Plasma amino acid levels were normal ( including glutamine, alanine, citrulline, arginine) and urine for organic acids were normal (Orotic acid, uracil). PCR showed a change in codon 208 of exon 6 from GCA to ACA, as happened in amniotic fluid of his grandsons.

These patients are relatively easy to treat once diagnosed, and no longer are the province of pediatric neurologists alone. PEARL-- female heterozygotes are often asymptomatic or minimally symptomatic.

Differential- of headache progressing tohyperammonemic coma can occur with any disorder of the urea cycle. Hyperammonemic citrin deficiency (citrullinemia type II) usually presents in adulthood, sometimes with sometimes without intrahepatic cholestasis and can result in death. Hyperammonemic coma can occur in hyperornithemia, as well. There are over 300 mutations known. Plasma amino acids can show elevated glutamine, alanine or aspartic acid. Citrulline may be low. Organic acids in the urine can show orotic acid or uracil high. Enzyme assay requires liver biopsy but 80 % of diagnoses are made by sequence analysis at this point.