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:
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
- 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
- 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
Kimiyo Raymond, M.D.
Consultant, Laboratory Genetics and Genomics
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science