Recommended Citation
Hoshaw R, Amendola L, Raquel C, Logsdon M. When Metabolism Meets Mind: The Diagnostic Challenges Behind Late-Onset OTC Deficiency. Presented at Scientific Day; May 20, 2026; Milwaukee, WI.
Abstract
Introduction/Background:
Ornithine transcarbamylase deficiency (OTCD) is the most prevalent urea cycle disorder (UCD), affecting ~1 in 60,000 people. As an X-linked condition, it was historically associated with severe neonatal disease in males. However, newer data shows females often present postnatally with highly variable symptoms and age of onset, frequently causing mis- or delayed diagnosis.
Description:
We report a case of a 10-year-old female with cyclic vomiting syndrome, attention deficit/hyperactivity disorder, and recent orthopedic surgery who presented with acute onset altered mental status, lethargy, and visual hallucinations without focal neurologic deficits on exam. Initial labs were notable for normal glucose and liver function tests (LFTs) without metabolic acidosis. She was admitted to the PICU and underwent extensive neurologic, infectious, and autoimmune evaluation notable for EEG with diffuse slowing, normal CSF studies, hyperammonemia (116 mcmol/L), and non-specific signaling abnormality on brain MRI. Repeat ammonia levels remained mildly elevated, thought to be due to hemolysis. Her mental status improved, and she was transferred to the floor. There, she developed multiple acute episodes of agitation. She had persistently elevated ammonia on free-flowing samples (114-159 mcmol/L) and undetectable BUN levels. Further history revealed long standing self-restriction of protein, learning difficulties in school, and history of “cyclic vomiting syndrome” that improved with dextrose containing fluids. Metabolics was consulted due to concern for UCD. She was started on high dextrose containing fluids, IV lipids, IV arginine, and lactulose. Ammonia levels continued to rise prompting transfer to quaternary care center with metabolic specialists. Genetic testing confirmed late-onset OTCD. Patient improved and was discharged following targeted nutritional and medical directed therapies for OTCD.
Discussion:
Diagnosing late-onset OTCD requires a high index of suspicion due to variable presentation. This case highlights confirmation bias, as elevated ammonia was initially attributed to hemolyzed samples in the setting of normal LFTs. Key diagnostic points from this case include altered mental status after surgery, hyperammonemia, low BUN, protein self-restriction, history of “cyclic vomiting syndrome,” and newborn screen with low-normal citrulline despite being reported as normal. Early recognition of OTCD is critical, as delayed diagnosis carries high morbidity and mortality.
Presentation Notes
Presented at Scientific Day; May 20, 2026; Milwaukee, WI.
Full Text of Presentation
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Document Type
Poster
Open Access
Available to all.
When Metabolism Meets Mind: The Diagnostic Challenges Behind Late-Onset OTC Deficiency
Introduction/Background:
Ornithine transcarbamylase deficiency (OTCD) is the most prevalent urea cycle disorder (UCD), affecting ~1 in 60,000 people. As an X-linked condition, it was historically associated with severe neonatal disease in males. However, newer data shows females often present postnatally with highly variable symptoms and age of onset, frequently causing mis- or delayed diagnosis.
Description:
We report a case of a 10-year-old female with cyclic vomiting syndrome, attention deficit/hyperactivity disorder, and recent orthopedic surgery who presented with acute onset altered mental status, lethargy, and visual hallucinations without focal neurologic deficits on exam. Initial labs were notable for normal glucose and liver function tests (LFTs) without metabolic acidosis. She was admitted to the PICU and underwent extensive neurologic, infectious, and autoimmune evaluation notable for EEG with diffuse slowing, normal CSF studies, hyperammonemia (116 mcmol/L), and non-specific signaling abnormality on brain MRI. Repeat ammonia levels remained mildly elevated, thought to be due to hemolysis. Her mental status improved, and she was transferred to the floor. There, she developed multiple acute episodes of agitation. She had persistently elevated ammonia on free-flowing samples (114-159 mcmol/L) and undetectable BUN levels. Further history revealed long standing self-restriction of protein, learning difficulties in school, and history of “cyclic vomiting syndrome” that improved with dextrose containing fluids. Metabolics was consulted due to concern for UCD. She was started on high dextrose containing fluids, IV lipids, IV arginine, and lactulose. Ammonia levels continued to rise prompting transfer to quaternary care center with metabolic specialists. Genetic testing confirmed late-onset OTCD. Patient improved and was discharged following targeted nutritional and medical directed therapies for OTCD.
Discussion:
Diagnosing late-onset OTCD requires a high index of suspicion due to variable presentation. This case highlights confirmation bias, as elevated ammonia was initially attributed to hemolyzed samples in the setting of normal LFTs. Key diagnostic points from this case include altered mental status after surgery, hyperammonemia, low BUN, protein self-restriction, history of “cyclic vomiting syndrome,” and newborn screen with low-normal citrulline despite being reported as normal. Early recognition of OTCD is critical, as delayed diagnosis carries high morbidity and mortality.
Affiliations
Advocate Children's Hospital