September 2021 – Biochemical Genetics

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. 

Resolution:

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

References

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