Genetics of Hyperammonemia Workup

Updated: Sep 20, 2018
  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

Plasma ammonia level

Obtain this measurement when clinical signs and symptoms are suggestive of hyperammonemia. Especially in the newborn, symptoms and signs suggestive of sepsis must always be accompanied by a plasma ammonia measurement, since the distinction between the two entities cannot be made by any clinical means and the presence of one does not preclude the other, in any case.

No other laboratory test can substitute for this measurement, nor does any other test indicate the need for it.

Only clinical suspicion indicates need.

Liver function studies (ie, serum transaminases, prothrombin time [PT]/activated partial thromboplastin time [aPTT]), alkaline phosphatase levels, bilirubin levels)

Severe liver disease can cause hyperammonemia; therefore, evaluating the function of the liver is always appropriate as a first approximation to etiology.

Plasma amino acid level quantitation

Certain primary genetic causes can be suspected based on specific increases in amino acid levels, such as increased citrulline or argininosuccinic acid levels.

By contrast, severe liver disease tends to cause a generalized increase in plasma amino acid levels.

Urinary organic acid profile

Disorders that involve metabolic intermediates of amino acid catabolism can cause mild-to-moderate inhibition of the urea cycle, resulting in hyperammonemia as a secondary phenomenon.

This test can help to identify increases in levels of such intermediates as propionic acid, methylmalonic acid, isovaleric acid, or other organic acids and aid in diagnosis.

Urine amino acid levels

These are helpful in confirming argininosuccinic aciduria; lysinuric protein intolerance; or hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome.

Blood lactate levels

This is useful in ruling out mitochondrial diseases, in some of which an elevated blood ammonia level may be found.

Blood gas levels

Patients with urea cycle disorders may have alkalosis due to stimulation of the respiratory drive by ammonia.

Patients with urea cycle disorders are rarely acidotic. Severe refractory acidosis suggests organic acid disorder or mitochondrial disorder.

BUN level

This is often very low (< 3 mg of urea/100 mL) in persons with urea cycle disorders.

N-carbamoyl-L-glutamic acid

In infants with confirmed hyperammonemia, oral loading with N -carbamoyl-L-glutamic acid has been advocated as both diagnostic and therapeutic for patients with N -acetylglutamate (NAG) synthetase deficiency.


Imaging Studies

Some authors advocate baseline MRI studies in patients with confirmed genetic causes of hyperammonemia; this is because some suggestive data indicate an elevated risk for stroke in these patients.