Abstract Details

Title Management and Progression of Arginase 1 Deficiency Over 2 Decades of Follow-up

Topic General Neurology

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 2-003

Background Arginase 1 Deficiency (ARG1-D) is a debilitating inborn error of metabolism with substantial, progressive morbidity driven by high arginine levels. Here, we describe an adult Caucasian male who presented to acute care at 3 years of age with new-onset seizures and a history of developmental delay.

Objective Not applicable

Design/Methods Not applicable

Results Liver function tests were remarkably elevated, and electroencephalography suggested diffuse cortical dysfunction; cognitive and motor delays and abnormal gait were evident. He was diagnosed with ARG1-D through amino acid testing (high arginine/low ornithine) and erythrocyte arginase activity (1% of normal control). He has received standard-of-care management with dietary protein restriction and nitrogen scavengers for >20 years, with ornithine to regenerate the urea cycle, botulinum toxin injections for severe contractures, and medication for seizures. Despite long-term treatment with the best-available care from a multispecialty team, plasma arginine remains high and unstable (initial on-treatment level, ~340 µmol/L; long-term range, 400-500 µmol/L). He has experienced chronic, debilitating progression with development of spastic quadriplegia by age 12, and cognitive impairment, recurrent seizures and vomiting, multiple hospitalizations for hyperammonemia, and hepatomegaly. The patient’s verbal ability and mobility improve when arginine levels trend lower; in contrast, episodes of irritability/aggression and loss of verbal ability coincide with higher arginine levels. Home care is required.

Conclusions The patient’s clinical course is consistent with the typical manifestations, natural history, and progressive nature of ARG1-D. This case illustrates the importance of high arginine in both chronic and acute ARG1-D manifestations and the limitations of available treatment, which does not sufficiently control arginine or prevent disease progression.

Authors/Disclosures
Deborah Marsden, MD (Department of Genetics and Genomics, Boston Children’s Hospital) PRESENTER	Dr. Marsden has received personal compensation for serving as an employee of Ultragenyx. Dr. Marsden has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Ultragenyx.
	No disclosure on file