Hyperammonemia in the Emergency Department

Case Histories

Hyperammonemia from a Urea Cycle Disorder Presenting in Adulthood
Tiffany C. Priester, Teck-Kim Khoo, Evans R. Fernández-Pérez, Kevin R. Regner,
Jennifer A. Tracy, Sabrina Mitchell, Marshall L. Summar and Dusica Babovic-Vuksanovic
The Open Critical Care Medicine Journal,2009, 2, 9-12

A 65-year-old woman presented to ED with severe progressive encephalopathy two days after uneventful abdominal hernia repair. Past history included 2 episodes of abdominal pain associated with vomiting that were assumed to be pancreatitis.

Findings: Serum ammonia 140 µMol/L, peak 490
  Respiratory alkalosis on spontaneous breathing
  No generalized liver dysfunction
Outcome: Expired day 10 in ICU
Final Dx: CPS1 deficiency

Fatal Initial Adult-Onset Presentation of Urea Cycle Defect

Jamie Lien, MD; William L. Nyhan, MD, PhD; Bruce A. Barshop, MD, PhD
Arch Neurol. 2007;64(12):1777-1779

A 52-year-old male awoke confused, ataxic and paranoid eight days after surgical removal of a throat polyp. He was taken to the ED after increasing disorientation and combativeness. Past history included type 2 diabetes, hypertension, hypercholesterolemia but considered to be in good health.

Findings: Serum ammonia 4202 µg/dL
  Negative transaminase enzyme
Outcome: Expired day 3 in ICU
Final Dx: OTC deficiency (dx made through heterozygous daughter)

Healthy, but Comatose
Brian Houston, Kim A. Reiss, Christian Merlo
The American Journal of Medicine,Volume 124, Issue 4 , Pages 303-305, April 2011

A 39-year-old previously healthy man was taken to the ED and admitted with contracted severe, acute pharyngitis. He was given cefuroximine and intravenous corticosteroids. He became confused, disoriented and progressively unresponsive. He was admitted to the ICU in coma. Past history was unremarkable except for a younger brother who had developed progressive severe confusion during an Outward Bound trip at the age of 14, causing the youth to run into a lake and drown.

Findings: Serum ammonia 249 µmol/L increasing to 438
  Mild respiratory alkalosis
  Negative toxicology
  Normal LFT
Outcome: Survival following rapid intervention by genetics team. Functionally independent with subtle cognitive deficits.
Final Dx: OTC deficiency

Unusual Causes of Hyperammonemia in the ED
Te-I Weng, Frank Fuh-Yuan Shih, Wen-Jone Chen. Am J Emerg Med. 2004 Mar;22(2):105-7

A 71-year-old woman presented to the ED after a one-day history of impaired consciousness. She was disoriented and confused in the ED, subsequently becoming comatose within 2 hours. Past history included several previous episodes of drowsiness and confusion in the past ten years which resolved spontaneously with supportive care alone.

Findings: Serum ammonia 133 µmol/L
Normal CBC, BUN, glucose, LFT
Outcome: Patient became vegetative as a result of aspiration pneumonia and hypoxic encephalopathy after receiving lactulose in the ED. Admitted to ICU with administration of sodium benzoate and sodium phenylacetate, citrulline and essential amino acids. She recovered consciousness after one month.
Final Dx: OTC deficiency

Adult onset ornithine transcarbamylase deficiency: an unusual cause of semantic disorders
S Rimbaux, C Hommet, D Perrier, J P Cottier, A Legras, F Labarthe, L Lemarcis, A Autret and F Maillot
J. Neurol. Neurosurg. Psychiatry 2004;75;1073-1075

A 21-year-old woman was admitted for a rapidly progressive coma following a several-day history of becoming unusually tired and disoriented. She developed inappropriate speech with acute delirium and had been hospitalized in a psychiatric institution, where her neurological status deteriorated to hypotonic coma. Her past medical history included an episode at age 12 of sleepiness with mental confusion, hypotonia, dysarthria, ataxia and vomiting; food poisoning was suspected after clinical signs resolved.

Findings: Serum ammonia 510 µmol/L
  Respiratory alkalosis
  Elevated urinary orotic acid
Outcome: Anterograde and retrograde amnesia. Language, reading and writing impairments. On long-term treatment with sodium phenylbutyrate, citrulline, low-protein diet.
Final Dx: OTC deficiency

Ornithine Transcarbamylase Deficiency Presenting as Encephalopathy During Adulthood Following Bariatric Surgery
William T. Hu, MD, PhD; Orhun H. Kantarci, MD; J. Lawrence Merritt II, MD; Pamela McGrann, MD;
P. James B. Dyck, MD; Claudia F. Lucchinetti, MD; Maja Tippmann-Peikert, MD
Arch Neurol. 2007;64:126-128

Six months following bariatric surgery, a 29-year-old became intermittently encephalopathic with somnolence, perseveration, echolalia and impaired short-term memory. Past history included an episode four weeks postsurgery of proximal, painful paresthesias in her legs, significant extremity weakness and confusion which was treated with IV thiamine replacement, but she continued to have fluctuating symptoms of mild encephalopathy.

Findings: Serum ammonia 42.3 µmol/L increasing to 91.6 (Subsequent labs in ICU found glutamine severely elevated at 2018 µmol/L)
  Markedly abnormal LFT
Outcome: Genetic testing for OTC mutations was negative, however, liver biopsy revealed <1% of normal OTC enzyme activity. After institution of treatment, serum ammonia and mental status normalized. After one year, her cognitive function continued stable without further episodes of encephalopathy.
Dx: OTC deficiency

Unmasked Adult-Onset Urea Cycle Disorders in the Critical Care Setting
Marshall L. Summar, Frederick Barr, Sheila Dawling, Wendy Smith, Brendan Lee, Rani H. Singh,William J. Rhead, Lisa Sniderman King, Brian W. Christman. Crit Care Clin 21 (2005) S1–S8

Case 1: A male in his early thirties presented to the ED after a four-wheeler accident with right clavicular and right tibial plateau fracture requiring ORIF. On the night following the surgery, he became confused and combative, with tachycardia, 106° hyperthermia, and generalized tonic-clonic seizures that the local hospital was unable to control, progressing to status epilepticus. His past medical history included closed head injury at 5 years of age with subsequent development of seizure disorder, well-controlled with carbamazepine and primidone. He had a history of hypertension, gastroesophageal reflux, persistent anemia and nonspecific psychiatric problems.
Findings: Serum ammonia 553 µmol at 24 hrs into course of coma
Outcome: Despite dialysis and 3 days of aggressive interventions, the patient developed pulmonary edema and was removed from life support.

Final Dx: NAGS deficiency determined by liver biopsy with enzymatic testing.
Summary: The patient’s multiple fractures triggered breakdown and processing of blood that was lost into the tissue surrounding the breaks, releasing large amounts of waste nitrogen which exceeded the clearance capacity of his underlying urea cycle enzyme function and unmasked the NAGS deficiency.

Case 2: A 58-year-old female with a history of recurrent episodes of “asthmatic bronchitis” presented to the ED with severe wheezing and productive cough of several days duration. Despite treatment with an aerosol bronchodilator, she continued to have bronchospasm and dyspnea with wheezes. The patient was admitted and intravenous steroids were initiated. On day five she developed acute confusion and expressive aphasia, progressing to coma within 48 hrs. She was thought to have steroid psychosis. Past history included recurrent episodes of asthma but no history of seizures or lethargy.

Findings: Serum ammonia 120 µmol/L increasing to 280
  Elevated glutamine, low citrulline and arginine
  Diffuse slowing on EEG; no seizure activity
Outcome: After treatment with dialysis, intravenous sodium phenylacetate/sodium benzoate, arginine and intravenous calories, the patient awoke within 8 hours and was discharged 3 days later. Followup over 5 years showed no residual deficits. Patient has not required dietary modification or oral nitrogen scavengers. Intravenous steroids were identified as the trigger of the event and have been avoided despite worsening asthma.
Final Dx: Symptomatic OTC carrier (patient had four male infant deaths from OTC deficiency; two adult OTC carrier daughters, one lost a male son and the other has a son with mild mental retardation and episodes of mild hyperammonemia in the past)
Summary: The intravenous steroids caused increased protein turnover, resulting in excessive nitrogen release.

More Cases Online

Hyperammonemic Coma in an Adult due to Ornithine Transcarbamylase Deficiency
Roberts DL, Galbreath DA, Patel BM, Ingall TJ, Khatib A, Johnson DJ. Case Reports in Critical Care
Volume 2013, Article ID 493216, 4 pages