eMedicine Specialties > Neurology > Neurotoxicology

Hyperammonemia: Differential Diagnoses & Workup

Author: Elena Crisan, MD, Consulting Staff, Department of Neurology, Edwards Hines Veterans Affairs Hospital
Coauthor(s): Jasvinder Chawla, MBBS, MD, MBA, Chief of Neurology, Hines Veterans Affairs Hospital; Associate Professor and Director, Neurology Residency Training Program, Loyola University Medical Center
Contributor Information and Disclosures

Updated: Aug 20, 2009

Differential Diagnoses

Ataxia with Identified Genetic and Biochemical Defects
Inherited Metabolic Disorders
Diseases of Tetrapyrrole Metabolism: Refsum Disease and the Hepatic Porphyrias
Metabolic Disease & Stroke: Homocystinuria/Homocysteinemia
Disorders of Carbohydrate Metabolism
Metabolic Disease & Stroke: Methylmalonic Acidemia
EEG in Dementia and Encephalopathy
Syncope and Related Paroxysmal Spells

Workup

Laboratory Studies

  • The following tests should be performed after a patient is found to be hyperammonemic:
    • Arterial blood gas analysis: This study determines acid-base status; respiratory alkalosis strongly suggests a urea cycle defect; it is the result of hyperventilation due to stimulation of the central respiratory drive.
    • Serum amino acid tests
      • Glutamine and alanine levels are increased in all urea cycle defects except for arginase deficiency.
      • Citrulline level is decreased mildly in CPS/NAGS and OTC deficiencies but increased markedly in AS deficiency and moderately in AL deficiency.
      • Arginine level is increased markedly in arginase deficiency but decreased mildly in all the other enzyme deficiencies of the urea cycle.
      • Argininosuccinic acid level is increased markedly in AL deficiency.
    • Urinary orotic acid tests: The level is increased markedly in OTC deficiency and mildly in other enzyme deficiencies except for CPS/NAGS deficiency, in which it is decreased mildly.
    • Urinary ketone tests: Presence of ketosis indicates an organic acidemia.
    • Plasma and urinary organic acid tests: These levels screen for the presence of an organic acidemia that may be causing the hyperammonemia.
    • Enzyme assays: Assays performed on tissue specimens obtained by percutaneous liver biopsy can determine diagnosis in cases of CPS, NAGS, and OTC deficiency.
  • Heterozygote identification in OTC-deficient pedigrees
    • Allopurinol loading test: This test establishes the carrier status of women at risk for OTC deficiency. After a loading dose of allopurinol, urinary orotidine excretion is measured; it is increased greatly in carriers.
    • DNA analysis: Several techniques are available to determine the presence of a mutation at the OTC locus.
  • Antenatal diagnosis: All urea cycle defects can be diagnosed antenatally by different techniques.

Imaging Studies

  • Neuroimaging: CT or MRI of the brain may show cerebral edema in acute hyperammonemia. The classic MR finding in patients with chronic liver disorders is hyperintense signal in the globus pallidum on T1 weighted images due to increased tissue concentration of manganese.   
  • MR spectroscopy: This shows an elevated glutamine/glutamate peak coupled with decreased myoinositol and choline signals.12,13
  • Multiple strokelike lesions have been recently reported as MRI finding in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria.14

Histologic Findings

The most consistent neuropathologic change in encephalopathies with hyperammonemia is prominent Alzheimer type II astrogliosis.

More on Hyperammonemia

Overview: Hyperammonemia
Differential Diagnoses & Workup: Hyperammonemia
Treatment & Medication: Hyperammonemia
Follow-up: Hyperammonemia
References
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References

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Further Reading

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Keywords

hyperammonemia, urea cycle disorders, urea cycle enzyme deficiencies, hepatic encephalopathies, Reye syndrome, toxic encephalopathies, metabolic disorders, ornithine transcarbamoylase deficiency, OTC deficiency, N -acetylglutamate synthetase deficiency, NAGS deficiency, carbamoyl phosphate synthetase I deficiency, carbamyl phosphate synthetase I deficiency, CPS I deficiency, argininosuccinic acid synthetase deficiency, AS deficiency, argininosuccinic lyase deficiency, AL deficiency, arginase deficiency, isovaleric acidemia, propionic acidemia, methylmalonic acidemia, glutaric acidemia type II, multiple carboxylase deficiency, beta-ketothiolase deficiency, congenital lactic acidosis, pyruvate dehydrogenase deficiency, pyruvate carboxylase deficiency, mitochondrial disorders, acyl CoA dehydrogenase deficiency, systemic carnitine deficiency, hyperammonemia-hyperornithinemia-homocitrullinuria, HHH

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Contributor Information and Disclosures

Author

Elena Crisan, MD, Consulting Staff, Department of Neurology, Edwards Hines Veterans Affairs Hospital
Elena Crisan, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Jasvinder Chawla, MBBS, MD, MBA, Chief of Neurology, Hines Veterans Affairs Hospital; Associate Professor and Director, Neurology Residency Training Program, Loyola University Medical Center
Jasvinder Chawla, MBBS, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Richard J Caselli, MD, Professor, Department of Neurology, Mayo Medical School, Rochester, MN; Chair, Department of Neurology, Mayo Clinic of Scottsdale
Richard J Caselli, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, American Neurological Association, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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