Abstract
Arginase 1 deficiency (ARG1D) is the least common urea cycle disorder. Neonatal onset is rarely described, and hyperammonemic coma is less common in patients with ARG1D compared to other urea cycle disorders. In recent years, we diagnosed a high number of ARG1D patients in Mayotte, an insular (Comoro Islands) department of France. This study aimed at retrospectively analyze and compare our patients' data with those diagnosed and followed in Paris. We present a series of 27 subjects included either in the Center Hospitalier de Mayotte (CHM), Mamoudzou, France (n = 17), or in Hôpital Necker-Enfants Malades (NEM), Paris, France (n = 10). Median age at diagnosis (n = 27) was 2 years (ranging from birth to 15 years). Patients diagnosed at CHM were generally older than those diagnosed at NEM, which may reflect a longer diagnostic delay in CHM. The main clinical features at diagnosis included hyperammonemic coma (with or without liver failure) and neurodevelopmental delay with spastic diplegia. Brain MRI could be either normal or showed severe lesions in patients with overt hyperammonemia at diagnosis. Eight different ARG1 variants were identified, including two variants (c.466-2 A>G and c.766G>A) that were found exclusively in subjects originating from the Comoro Islands. Despite no significant differences in laboratory parameters, clinical outcomes remained better in NEM versus CHM possibly ascribable to a longer diagnostic delay in CHM. These findings revealed a new cluster of ARG1D associated with two severe variants in Mayotte, suggesting that this region could possibly benefit from targeted newborn screening for ARG1D due to its overrepresentation.