September 2021 – Biochemical Genetics

A 13-month-old girl presents with recurrent vomiting for three months. Her labs are significant for elevated AST, ALT, and alkaline phosphatase and prolonged INR (not specified).

Ammonia = 200 (≤80 mcmol/L) 

Lactate = 22 (normal <19mg/dL)

Amino acid panel and urine organic acid analysis showed the following:

Table 1
Table 2

Which urea cycle disorder is the most likely diagnosis?

  • N-acetylglutamate synthetase deficiency (NAGS)
  • Ornithine Transcarbamylase deficiency (OTC)
  • Carbamoyl Phosphate Synthethase deficiency (CPSI)
  • Arginosuccinate Synthase 1 Deficiency (ASS1)

The correct answer is ...

The correct answer is: Ornithine Transcarbamylase deficiency (OTC).

Ammonia levels above 200 umol/L suggests an enzyme early in the urea cycle. 

Quantitative analysis of amino acids (AA) performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed elevated glutamine and alanine, low arginine and citrulline.

Urine organic acids analysis showed high levels of orotic acid excretion (332 mmol/mol creatinine; reference values: <4) and uracil. There were no other unusual organic acids. 


OTC diagnosis was confirmed. Arginine supplementation and hydration were advised. 

Ornithine transcarbamylase (OTC) deficiency is a rare, X-linked genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase (OTC) in which hemizygous males are almost always symptomatic and about 20% of female carriers, may present some neurocognitive deficit.

OTC is the most frequent cause of UCD, accounting for nearly 50% of all cases. OTC deficiency is the most common inherited disease of ureagenesis, with an estimated prevalence of 1 in 62,000 to 1 in 77,000


  1. Rush, Eric T et al. “Late-onset ornithine transcarbamylase deficiency: An under recognized cause of metabolic encephalopathy.” SAGE open medical case reports vol. 2 2050313X14546348. 31 Jul. 2014, doi:10.1177/2050313X14546348
  2. Savy, Nadia et al. “Acute pediatric hyperammonemia: current diagnosis and management strategies.” Hepatic medicine : evidence and research vol. 10 105-115. 12 Sep. 2018, doi:10.2147/HMER.S140711

Paola Ramos, Ph.D.

Fellow, Clinical Chemistry
Mayo Clinic

Kimiyo Raymond, M.D. 

Consultant, Laboratory Genetics and Genomics
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.