ABSTRACT
The urea cycle disorder argininemia is caused by a defective arginase 1 (ARG1) enzyme resulting from mutations in the ARG1 gene. Patients generally develop hyperargininemia, spastic paraparesis, progressive neurological and intellectual impairment, and persistent growth retardation. Interestingly, in contrast to other urea cycle disorders, hyperammonemia is rare. We report here 66 mutations (12 of which are novel), including 30 missense mutations, seven nonsense, 10 splicing, 15 deletions, two duplications, one small insertion, and one translation initiation codon mutation. For the most common mutations (p.Thr134Ile, p.Gly235Arg and p.Arg21*), which cluster geographically in Brazil, China, or Turkey, a structural rationalization of their effect has been included. In order to gain more knowledge on the disease, we have collected clinical and biochemical information of 112 patients, including the patients' genetic background and ethnic origin. We have listed as well the missense variants with unknown relevance. For all missense variants (of both known and unknown relevance), the conservation, severity prediction, and ExAc scores have been included. Lastly, we review ARG1 regulation, animal models, diagnostic strategies, newborn screening, prenatal testing, and treatment options.