Ornithine Transcarbamylase (OTC) Deficiency Workup

Updated: Jan 07, 2019
  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Laboratory Studies

In an individual with ornithine transcarbamylase (OTC) deficiency, the sine qua non of diagnosis is demonstration of hyperammonemia.

As in CPS deficiency, routinely obtained blood chemistries are not helpful, although a very low BUN level may present a diagnostic clue. This should not be interpreted as a substitute for blood ammonia studies because it is not sufficiently reliable.

Liver and kidney function typically remain normal unless hypoxia or shock supervenes. However, exceptions have been noted.

Serum amino acid quantitation may show elevated ornithine, glutamine, and alanine levels and relatively low citrulline levels, but these changes are neither invariable nor diagnostic. Urine organic acid and amino acid analysis are helpful in ruling out other conditions.

Beyond demonstration of hyperammonemia, the only basis for clinical diagnosis is demonstration of elevated urinary orotic acid. This test also can be used, under appropriate conditions, to detect asymptomatic carriers.

Remember that ornithine transcarbamylase is a mitochondrial hepatic enzyme and is subject to rapid postmortem degradation. Therefore, perform any liver biopsy prior to or immediately after death and properly handle the specimen in order to avoid artifactual diagnosis of deficiency. Experienced diagnostic laboratories perform control assays of nonlabile hepatic enzymes, but this cannot substitute for proper sampling and handling. Hepatic biopsy and enzyme analysis have been replaced by mutational analysis, thus reducing the risk to the affected infant.


Other Tests

Enzymatic deficiency of the ornithine transcarbamylase enzyme has been supplanted by molecular diagnosis. However, even using a combination of different molecular analytic strategies, only 80% of proven enzymatic deficiencies can be shown to have genetic mutation.

The reasons for this inconsistency remain elusive. However, molecular techniques are very useful for prenatal diagnosis, especially when the specific mutation in the pedigree has been previously documented.