Dietary protein is metabolized and then excreted as urea via the urea cycle. Urea cycle enzymatic deficiencies are usually inherited and rare, and generally present in newborns. We present a case of carbamyl phosphate synthetase deficiency in an elderly woman admitted to the intensive care unit (ICU) for decreased consciousness with hyperammonemia.
A 65 year old woman was transferred to our institution soon after abdominal hernia repair surgery in an outside hospital with severe progressive decrease in mentation. On presentation, her Glasgow Coma score was 3, and she was endotracheally intubated for airway protection. Her past medical history was significant for two previous unexplained episodes of nausea and nonspecific abdominal pain associated with vomiting. On admission to the ICU, she was unresponsive without focal neurological abnormalities. Her admission blood ammonia level was 196 μmol/L (normal for our laboratory is 10 to 47 μmol/L) and increased to 305 μmol/L the following day. Other laboratory studies including liver transaminases, creatinine and spinal fluid were normal. CT of the head was unremarkable and CT of the abdomen and pelvis disclosed changes suggestive of fatty liver. A urea cycle disorder was suspected. The serum amino acid panel demonstrated high plasma glutamine levels (5531 μmol/L; reference range: 205-756 μmol/L). Because of the persistent hyperammonemia and lack of improvement in mental status, she was initiated on a low-protein enteral diet and hemodialysis. With dialysis, her ammonia level decreased to 86 μmol/L. However, she remained unconscious and showed no sign of improvement. On day 7 of ICU stay, she developed ventilator-associated pneumonia, growing methicillin-sensitive staphylococcus aureus. Blood cultures also grew a gram-negative bacillus. Antimicrobial therapy was initiated. Because of the lack of clinical improvement, the family decided to withdraw therapy. Hemodialysis was discontinued and her ammonia increased to a high of 686 μmol/L. On day 10 of hospital stay, she passed away. A transcutaneous needle biopsy was obtained which provided the diagnosis of partial carbamyl phosphate synthetase I (CPSI) deficiency.
CPSI is the first enzyme involve in conversion of ammonia to urea through the urea cycle. Partial enzyme deficiencies may present in late adulthood as seen in our patient. CPSI deficiency can present at almost any time of life with a stressful triggering events. Prevention of systemic stress and early intervention of hyperammonemic crisis is paramount. Clinical features include nausea, vomiting, somnolence and seizures. Neurologic symptomatology has been linked to cerebral injury during hyperammonemic crisis which is associated with glutamine accumulation. Intratraneuronal glutamine may serve as an osmole causing alterations in neurotransmitter metabolism and brain swelling (1). The diagnosis is based on enzymatic assay of liver tissue and treatment involves nitrogen restriction and enhancement of nitrogen excretion using sodium benzoate or phenylbutyrate. Continuous arteriovenous or venovenous hemodialysis (HD) at high flow rates should be started in the setting of severe hyperammonemia or absence of clinical improvement. HD is continued until the ammonia concentration is lower than 200 μmol/L. Below this level HD appears to be of no benefit. Alternatively, successful treatment with orthotopic liver transplantation has also been described in the literature.
Urea cycle disorders should be part of the differential diagnosis of isolated hyperammonemia if no obvious cause is identified regardless of the patient’s age. Hyperammonemic encephalopathy may result in severe brain dysfunction and a rapidly fatal course. A high degree of clinical alertness is a prerequisite since prompt diagnosis and treatment may be of benefit in CPSI deficiency before brain injury develops.
Teck-Kim Khoo, None.