OBJECTIVES: Arginase 1 Deficiency (ARG1-D) is an inherited, metabolic urea cycle disorder characterized by persistent elevation of arginine and its metabolites, and debilitating and progressive clinical manifestations. The objective of this study was to systematically review the literature to assess the epidemiology, methods of diagnosis, and clinical management of patients with ARG1-D.

METHODS: MEDLINE, EMBASE, and other databases were searched and eligible studies reporting the epidemiology (incidence/prevalence, patient demographics), diagnosis methods, and/or clinical management (type of treatments, outcomes) of ARG1-D were analyzed. Two individuals independently screened records, extracted data, and assessed study quality using the Newcastle-Ottawa Scale (NOS).

RESULTS: We included 40 studies of good quality (based on NOS) that described 291 ARG1-D patients. The median prevalence of ARG1-D was 1 per 1,000,000 births (9 studies). Elevated plasma arginine was the most commonly reported method of diagnosis (22/37 studies), followed by the absence of red blood cell arginase (16/37 studies), and genetic testing (12/37 studies); 12 studies included newborn screening. Reported measures of disease progression were variable across studies: motor function/mobility, including spasticity, was the most common manifestation reported (14/18 studies), followed by intellectual disability (12/18), seizures (9/18), and developmental delay (8/18). In studies reporting dietary treatments, 95% of patients were on protein-restrictive diets (10 studies); 62% of patients used nitrogen scavengers (12 studies), and 45% of patients used essential amino acid supplements (6 studies). The most commonly assessed outcomes were intellectual disability, motor function, and mortality.

CONCLUSIONS: Although there is variation in the methods of diagnosing, assessing, and treating ARG1-D, this review found that ARG1-D is a debilitating, progressive, inherited, metabolic disorder with simple methods of diagnosis. ARG1-D specific guidelines on diagnosis and treatment are needed to encourage early detection and effective management to prevent or minimize the manifestations of the disease.