Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centre

Abstract

AbstractBackgroundThe clinical presentation of ARG1‐D is characterised by elevated arginine levels leading to neurological and mobility impairments. Information about long‐term outcomes in adults is lacking, which prompted us to undertake a retrospective observational study.MethodsWe extracted ARG1‐D patient data spanning a 5‐year period from electronic health records. Ethical approval was not required for the study. Informed consent was obtained.ResultsWe identified nine ARG1‐D patients from consanguineous backgrounds. Age of symptom onset ranged from infancy to age 7 years, age of diagnosis from infancy to 20 years. Patients had paraparesis or altered gait of varying degree and had experienced early ARG1‐D onset. Over 5 years, mobility declined in six (6/9, 67%) patients. Three patients (3/9, 33%) were fully dependent and hoisted. Two (2/9, 22%) reached adulthood before experiencing hyperammonaemia, another one (1/9, 11%) first experienced hyperammonaemia at age 15 years. One patient (1/9, 11%) started on ammonia scavenger therapy in adulthood, one (1/9, 11%) required a second scavenger to be added to their treatment regimen. Two patients (2/9, 22%) had gastrostomy tubes inserted for nutrition and supplements at age 9 years and 15 years. Six patients (6/9, 67%) had raised levels of ALT; of these, four (4/9, 44%) also had elevated AFP. Heterogeneity of ARG1‐D symptoms was evident, suggesting complex genetic and environmental interactions.ConclusionARG1‐D presents significant lifelong challenges with deteriorating mobility and more frequent metabolic crises. Current management strategies are insufficient for preventing progression, highlighting the need for innovative treatments like enzyme replacement and gene therapy.